Concentration Enrichment in a Dissolving Microdroplet: Accessing Sub-nanomolar Electroanalysis.

Droplet evaporation has previously been used as a concentration enrichment strategy; however, the measurement technique of choice requires quantification in rather large volumes. Electrochemistry has recently emerged as a method to robustly probe volumes even down to the attoliter (10-18 L) level. We present a concentration enrichment strategy based on the dissolution of a microdroplet placed on the surface of a Au ultramicroelectrode (radius ∼ 6.25 µm). By precisely positioning a 1,2-dichloroethane microdroplet onto the ultramicroelectrode with a microinjector, we are able to track the droplet's behavior optically and electrochemically. Because the droplet spontaneously dissolves over time, given the relative solubility of 1,2-dichloroethane in the water continuous phase, the change in volume with time enriches the concentration of the redox probe (Cp2*(Fe)II) in the droplet. We demonstrate robust electrochemical detection down to sub-nM (800 pM) concentrations of Cp2*(Fe)II. For this droplet, 800 pM constitutes only about 106 molecules. We extend the strategy in a single-blind study to determine unknown concentrations, emphasizing the promise of the new methodology. These results take voltammetric quantification easily to the sub-µM regime.

Chemoenzymatic Synthesis of Select Intermediates and Natural Products of the Desferrioxamine E Siderophore Pathway.

The NIS synthetase family of enzymes responsible for the biosynthesis of siderophores is increasingly associated with bacterial virulence. Proteins in this class represent outstanding potential drug targets, assuming that basic biochemical and structural characterizations can be completed. Towards this goal, we have mated an improved synthesis of the non-commercial amino acid N-hydroxy-N-succinylcadaverine (HSC, 6) with an isothermal titration calorimetry (ITC) assay that profiles the iterative stages of HSC trimerization and macrocyclization by NIS synthetase DesD from Streptomyces coelicolor. HSC synthesis begins with multigram-scale Gabrielle and tert-butyl N-(benzyloxy)carbamate alkylations of 1-bromo-5-chloropentane following prior literature, but the end-game reported herein has two advantages for greater material throughput: (1) hydrogenolysis of benzyl ether and Cbz blocking groups is best accomplished with Pearlman's catalyst at 40 psi of H2 and (2) purification of neutral (zwitterionic) HSC is effected by simple flash chromatography over silica gel in MeOH. HSC is subsequently shown to be a substrate for NIS synthetase DesD, which catalyzes three successive amide bond syntheses via adenyl monophosphate ester intermediates. We quantify and present the iterative and overall enzyme kinetic constants associated with formation of the cyclotrimeric siderophore desferrioxamine E (dfoE, 1).

Coronal Correction Using Kickstand Rods for Adult Thoracolumbar/Lumbar Scoliosis: Case Series With Analysis of Early Outcomes and Complications.

BACKGROUND: The "kickstand rod technique" has been recently described for achieving and maintaining coronal correction in adult spinal deformity (ASD). Kickstand rods span scoliotic lumbar spine from the thoracolumbar junction proximally to a "kickstand iliac screw" distally. Using the iliac wing as a base, kickstand distraction produces powerful corrective forces. Limited literature exists for this technique, and its associated outcomes and complications are unknown. OBJECTIVE: To assess alignment changes, early outcomes, and complications associated with kickstand rod distraction for ASD. METHODS: Consecutive ASD patients treated with kickstand distraction at our institution were retrospectively analyzed. RESULTS: The cohort comprised 19 patients (mean age: 67 yr; 79% women; 63% prior fusion) with mean follow-up 21 wk (range: 2-72 wk). All patients had posterior-only approach surgery with tri-iliac fixation (third iliac screw for the kickstand) for mean fusion length 12 levels. Three-column osteotomy and lumbar transforaminal lumbar interbody fusion were performed in 5 (26%) and 15 (79%) patients, respectively. Postoperative alignment improved significantly (coronal balance: 8 to 1 cm [P < .001]; major curve: 37° to 12° [P < .001]; fractional curve: 20° to 10° [P < .001]; sagittal balance: 11 to 4 cm [P < .001]; pelvic incidence to lumbar lordosis mismatch: 38° to 9° [P < .001]). Pain Numerical Rating Scale scores improved significantly (back: 7.2 to 4.2 [P = .001]; leg: 5.9 to 1.7 [P = .001]). No instrumentation complications occurred. Motor weakness persisted in 1 patient. There were 3 reoperations (1-PJK, 1-wound dehiscence, and 1-overcorrection). CONCLUSION: Among 19 ASD patients treated with kickstand rod distraction, alignment, and back/leg pain improved significantly following surgery. Complication rates were reasonable.

Postoperative pyoderma gangrenosum after spinal fusion with instrumentation: case report.

Pyoderma gangrenosum (PG) is a rare inflammatory dermatosis that is most often associated with inflammatory bowel disease, but which can occur as a pathergic reaction around surgical incisions. The authors report the case of a patient who developed postoperative PG over the course of several months after undergoing extensive spinal instrumentation between the T4 and iliac levels. This is only the second such case occurring after spine surgery to be reported. The authors additionally review the literature to characterize treatment approaches and outcomes for this condition. The case highlights a potentially severe adverse effect of surgery that can be difficult to recognize and causes delays in effective treatment. It also demonstrates the importance of multidisciplinary collaboration in the effective care of patients.

Surgical correction of severe adult lumbar scoliosis (major curves ≥ 75°): retrospective analysis with minimum 2-year follow-up.

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.

Low rates of complications after spinopelvic fixation with iliac screws in 260 adult patients with a minimum 2-year follow-up.

OBJECTIVERecent literature describing complications associated with spinopelvic fixation with iliac screws in adult patients has been limited but has suggested high complication rates. The authors' objective was to report their experience with iliac screw fixation in a large series of patients with a 2-year minimum follow-up.METHODSOf 327 adult patients undergoing spinopelvic fixation with iliac screws at the authors' institution between 2010 and 2015, 260 met the study inclusion criteria (age ≥ 18 years, first-time iliac screw placement, and 2-year minimum follow-up). Patients with active spinal infection were excluded. All iliac screws were placed via a posterior midline approach using fluoroscopic guidance. Iliac screw heads were deeply recessed into the posterior superior iliac spine. Clinical and radiographic data were obtained and analyzed.RESULTSTwenty patients (7.7%) had iliac screw-related complication, which included fracture (12, 4.6%) and/or screw loosening (9, 3.5%). No patients had iliac screw head prominence that required revision surgery or resulted in pain, wound dehiscence, or poor cosmesis. Eleven patients (4.2%) had rod or connector fracture below S1. Overall, 23 patients (8.8%) had L5-S1 pseudarthrosis. Four patients (1.5%) had fracture of the S1 screw. Seven patients (2.7%) had wound dehiscence (unrelated to the iliac screw head) or infection. The rate of reoperation (excluding proximal junctional kyphosis) was 17.7%. On univariate analysis, an iliac screw-related complication rate was significantly associated with revision fusion (70.0% vs 41.2%, p = 0.013), a greater number of instrumented vertebrae (mean 12.6 vs 10.3, p = 0.014), and greater postoperative pelvic tilt (mean 27.7° vs 23.2°, p = 0.04). Lumbosacral junction-related complications were associated with a greater mean number of instrumented vertebrae (12.6 vs 10.3, p = 0.014). Reoperation was associated with a younger mean age at surgery (61.8 vs 65.8 years, p = 0.014), a greater mean number of instrumented vertebrae (12.2 vs 10.2, p = 0.001), and longer clinical and radiological mean follow-up duration (55.8 vs 44.5 months, p < 0.001; 55.8 vs 44.6 months, p < 0.001, respectively). On multivariate analysis, reoperation was associated with longer clinical follow-up (p < 0.001).CONCLUSIONSPrevious studies on iliac screw fixation have reported very high rates of complications and reoperation (as high as 53.6%). In this large, single-center series of adult patients, iliac screws were an effective method of spinopelvic fixation that had high rates of lumbosacral fusion and far lower complication rates than previously reported. Collectively, these findings argue that iliac screw fixation should remain a favored technique for spinopelvic fixation.

Alignment Risk Factors for Proximal Junctional Kyphosis and the Effect of Lower Thoracic Junctional Tethers for Adult Spinal Deformity.

OBJECTIVE: The aims of this retrospective cohort study were to 1) identify new alignment risk factors for proximal junctional kyphosis (PJK) in adult spinal deformity (ASD) patients with lower thoracic upper instrumented vertebra (UIV) and 2) determine the effect of junctional tethers on PJK and UIV alignment. METHODS: We analyzed consecutive ASD patients who underwent posterior instrumented fusion with lower thoracic UIV (T9-T11). Posteriorly anchored junctional tethers were used more recently for ligamentous augmentation to prevent PJK. In addition to regional and global parameters, upper segmental lumbar lordosis (ULL) versus lower segmental lumbar lordosis and UIV angle (measured from UIV inferior endplate to horizontal) were assessed. Primary outcome of PJK was defined as proximal junctional angle >10° and >10° greater than the corresponding preoperative measurement. Univariable and multivariable analyses were performed. RESULTS: The study cohort comprised 120 ASD patients (mean age, 67 years) with minimum 1-year follow-up. Preoperative ULL (P = 0.034) and UIV angle (P = 0.026) were associated with PJK. No independent preoperative alignment risk factors of PJK were identified in multivariable analysis. Tether use was protective against PJK (odds ratio, 0.063 [0.016-0.247]; P < 0.001). PJK in tethered patients was more common with greater postoperative ULL (P = 0.047) and UIV angle (P = 0.026). CONCLUSIONS: Junctional tethers significantly reduced PJK in ASD patients with lower thoracic UIV. In tethered patients, PJK was more common with greater postoperative lordosis of the upper lumbar spine and greater UIV angle. This finding suggests potential benefit of tethers to mitigate effects of segmental lumbar and focal UIV malalignment that may occur after deformity surgery.

A Novel Junctional Tether Weave Technique for Adult Spinal Deformity: 2-Dimensional Operative Video.

Proximal junctional kyphosis (PJK) is a common problem after multilevel spine instrumentation for adult spinal deformity. Various anti-PJK techniques such as junctional tethers for ligamentous augmentation have been proposed. We present an operative video demonstrating technical nuances of junctional tether "weave" application. A 70-yr-old male with prior L2-S1 instrumented fusion presented with worsening back pain and posture. Imaging demonstrated pathological loss of lumbar lordosis (flat back deformity), proximal junctional failure, and pseudarthrosis. The patient had severe global and segmental sagittal malalignment, with sagittal vertical axis (SVA, C7-plumbline) measuring 22.3 cm, pelvic incidence (PI) 55°, lumbar lordosis (LL) 8° in kyphosis, pelvic tilt (PT) 30°, and thoracic kyphosis (TK) 6°. The patient gave informed consent for surgery and use of imaging for medical publication. Briefly, surgery first involved re-instrumentation with bilateral pedicle screws from T10 to S1. After right-sided iliac screw fixation (left-sided iliac screw fixation was not performed due to extensive prior iliac crest bone graft harvesting), we then completed a L2-3 Smith-Petersen osteotomy, extended L4 pedicle subtraction osteotomy, and L3-4 interbody arthrodesis with a 12° lordotic cage (9 × 14 × 40 mm). Cobalt Chromium rods were placed spanning the instrumentation bilaterally, and accessory supplemental rods spanning the PSO were attached. An anti-PJK junctional tether "weave" was then implemented using 4.5 mm polyethylene tape (Mersilene tape [Ethicon, Somerville, New Jersey]). Postoperative imaging demonstrated improved alignment (SVA 2.8 cm, PI 55°, LL 53°, PT 25°, TK 45°) and no significant neurological complications occurred during convalescence or at 6 mo postop.

Neoplastic Cerebral Aneurysm from Metastatic Lung Adenocarcinoma with Neuroendocrine Features.

BACKGROUND: Neoplastic cerebral aneurysms are exceedingly rare. We describe a case of a ruptured, distal middle cerebral artery aneurysm as the presenting symptom leading to the identification of metastatic lung cancer. CASE DESCRIPTION: The patient underwent an uncomplicated surgical trapping and ligation of the aneurysm. Histopathologic examination of the aneurysm confirmed the neoplastic cerebral aneurysm was due to a metastatic lung adenocarcinoma with neuroendocrine features. The patient subsequently underwent stereotactic radiosurgery to the resection cavity. CONCLUSIONS: Neoplastic cerebral aneurysms are rare, and there are insufficient data to support specific guidelines for management. This case is novel as the patient received adjuvant stereotactic radiosurgery to the operative bed, as well as systemic chemotherapy, and has maintained good functional status as of last follow-up at 6 months.

Presentation and Outcomes After Medical and Surgical Treatment Versus Medical Treatment Alone of Spontaneous Infectious Spondylodiscitis: A Systematic Literature Review and Meta-Analysis.

STUDY DESIGN: Systematic literature review. OBJECTIVES: The aims of this study were to (1) describe the clinical features, disabilities, and incidence of neurologic deficits of pyogenic spondylodiscitis prior to treatment and (2) compare the functional outcomes between patients who underwent medical treatment alone or in combination with surgery for pyogenic spondylodiscitis. METHODS: A systematic literature review was performed using PubMed according to PRISMA guidelines. No year restriction was put in place. Statistical analysis of pooled data, when documented in the original report (ie, number of patients with desired variable and number of patients evaluated), was conducted to determine the most common presenting symptoms, incidence of pre- and postoperative neurologic deficits, associated comorbidities, infectious pathogens, approach for surgery when performed, and duration of hospitalization. Outcomes data, including return to work status, resolution of back pain, and functional recovery were also pooled among all studies and surgery-specific studies alone. Meta-analysis of studies with subgroup analysis of pain-free outcome in surgical and medical patients was performed. RESULTS: Fifty of 1286 studies were included, comprising 4173 patients undergoing either medical treatment alone or in combination with surgery. Back pain was the most common presenting symptom, reported in 91% of patients. Neurologic deficit was noted in 31% of patients. Staphylococcus aureus was the most commonly reported pathogen, seen in 35% of reported cases. Decompression and fusion was the most commonly reported surgical procedure, performed in 80% of the surgically treated patients. Combined anterior-posterior procedures and staged surgeries were performed in 33% and 26% of surgeries, respectively. The meta-analysis comparing visual analog scale score at follow-up was superior among patients receiving surgery over medical treatment alone (mean difference -0.61, CI -0.90 to -0.25), while meta-analysis comparing freedom from pain in patients receiving medical treatment alone versus combined medical and surgical treatment demonstrated superior pain-free outcomes among surgical series (odds ratio 5.35, CI 2.27-12.60, P < .001), but was subject to heterogeneity among studies (I 2 = 56%, P = .13). Among all patients, freedom from pain was achieved in 79% of patients, and an excellent outcome was achieved in 73% of patients. CONCLUSION: Medical management remains first-line treatment of infectious pyogenic spondylodiscitis. Surgery may be indicated for progressive pain, persistent infection on imaging, deformity or neurologic deficits. If surgery is required, reported literature shows potential for significant pain reduction, improved neurologic function and a high number of patients returning to a normal functional/work status.

Radiographic outcome and complications after single-level lumbar extended pedicle subtraction osteotomy for fixed sagittal malalignment: a retrospective analysis of 55 adult spinal deformity patients with a minimum 2-year follow-up.

OBJECTIVEFixed sagittal spinal malalignment is a common problem in adult spinal deformity (ASD). Various three-column osteotomy techniques, including the extended pedicle subtraction osteotomy (ePSO), may correct global and regional malalignment in this patient population. In contrast to the number of reports on traditional PSO (Schwab grade 3 osteotomy), there is limited literature on the outcomes of ePSO (Schwab grade 4 osteotomy) in ASD surgery. The objective of this retrospective study was to provide focused investigation of radiographic outcomes and complications of single-level lumbar ePSO for ASD patients with fixed sagittal malalignment.METHODSConsecutive ASD patients in whom sagittal malalignment had been treated with single-level lumbar ePSO at the authors' institution between 2010 and 2015 were analyzed, and those with a minimum 2-year follow-up were included in the study. Radiographic analyses included assessments of segmental lordosis through the ePSO site (sagittal Cobb angle measured from the superior endplate of the vertebra above and inferior endplate of the vertebra below the ePSO), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence and LL mismatch, thoracic kyphosis (TK), and sagittal vertical axis (SVA) on standing long-cassette radiographs. Complications were analyzed for the entire group.RESULTSAmong 71 potentially eligible patients, 55 (77%) had a minimum 2-year follow-up and were included in the study. Overall, the average postoperative increases in ePSO segmental lordosis and overall LL were 41° ± 14° (range 7°-69°, p < 0.001) and 38° ± 11° (range 9°-58°, p < 0.001), respectively. The average SVA improvement was 13 ± 7 cm (range of correction: -33.6 to 3.4 cm, p < 0.001). These measurements were maintained when comparing early postoperative to last follow-up values, respectively (mean follow-up 52 months, range 26-97 months): ePSO segmental lordosis, 34° vs 33°, p = 0.270; LL, 47.3° vs 46.7°, p = 0.339; and SVA, 4 vs 5 cm, p = 0.330. Rod fracture (RF) at the ePSO site occurred in 18.2% (10/55) of patients, and pseudarthrosis (PA) at the ePSO site was confirmed by CT imaging or during rod revision surgery in 14.5% (8/55) of patients. Accessory supplemental rods across the ePSO site, a more recently employed technique, significantly reduced the occurrence of RF or PA on univariate (p = 0.004) and multivariable (OR 0.062, 95% CI 0.007-0.553, p = 0.013) analyses; this effect approached statistical significance on Kaplan-Meier analysis (p = 0.053, log-rank test). Interbody cage placement at the ePSO site resulted in greater ePSO segmental lordosis correction (45° vs 35°, p = 0.007) without significant change in RF or PA (p = 0.304). Transient and persistent motor deficits occurred in 14.5% (8/55) and 1.8% (1/55) of patients, respectively.CONCLUSIONSExtended PSO is an effective technique to correct fixed sagittal malalignment for ASD. In comparison to traditional PSO techniques, ePSO may allow greater focal correction with comparable complication rates, especially with interbody cage placement at the ePSO site and the use of accessory supplemental rods.

Gamma Knife radiosurgery of large skull base meningiomas.

OBJECT: Stereotactic radiosurgery (SRS) has become a common treatment modality for intracranial meningiomas. Skull base meningiomas greater than 8 cm3 in volume have been found to have worse outcomes following SRS. When symptomatic, patients with these tumors are often initially treated with resection. For tumors located in close proximity to eloquent structures or in patients unwilling or unable to undergo a resection, SRS may be an acceptable therapeutic approach. In this study, the authors review the SRS outcomes of skull base meningiomas greater than 8 cm3 in volume, which corresponds to a lesion with an approximate diameter of 2.5 cm. METHODS: The authors reviewed the data in a prospectively compiled database documenting the outcomes of 469 patients with skull base meningiomas treated with single-session Gamma Knife radiosurgery (GKRS). Seventy-five patients had tumors greater than 8 cm3 in volume, which was defined as a large tumor. All patients had a minimum follow-up of 6 months, but patients were included if they had a complication at any time point. Thirty patients were treated with upfront GKRS, and 45 were treated following microsurgery. Patient and tumor characteristics were assessed to determine predictors of new or worsening neurological function and tumor progression following GKRS. RESULTS: After a mean follow-up of 6.5 years (range 0.5-21 years), the tumor volume was unchanged in 37 patients (49%), decreased in 26 patients (35%), and increased in 12 patients (16%). Actuarial rates of progression-free survival at 3, 5, and 10 years were 90.3%, 88.6%, and 77.2%, respectively. Four patients had new or worsened edema following GKRS, but preexisting edema decreased in 3 patients. In Cox multivariable analysis, covariates associated with tumor progression were 1) presentation with any cranial nerve (CN) deficit from III to VI (hazard ratio [HR] 3.78, 95% CI 1.91-7.45; p<0.001), history of radiotherapy (HR 12.06, 95% CI 2.04-71.27; p=0.006), and tumor volume greater than 14 cm3 (HR 6.86, 95% CI 0.88-53.36; p=0.066). In those patients with detailed clinical follow-up (n=64), neurological function was unchanged in 37 patients (58%), improved in 16 patients (25%), and deteriorated in 11 patients (17%). In multivariate analysis, the factors predictive of new or worsening neurological function were history of surgery (OR 3.00, 95% CI 1.13-7.95; p=0.027), presentation with any CN deficit from III to VI (OR 3.94, 95% CI 1.49-10.24; p=0.007), and decreasing maximal dose (OR 0.76, 95% CI 0.63-0.93; p=0.007). Tumor progression was present in 64% of patients with new or worsening neurological decline. CONCLUSIONS: Stereotactic radiosurgery affords a reasonable rate of tumor control for large skull base meningiomas and does so with a low incidence of neurological deficits. Those with a tumor less than 14 cm3 in volume and without presenting CN deficit from III to VI were more likely to have effective tumor control.

Multisession gamma knife radiosurgery: a preliminary experience with a noninvasive, relocatable frame.

OBJECTIVE: To evaluate preliminary outcomes for a cohort of patients who were treated with multisession Gamma Knife radiosurgery (GKRS) using the new noninvasive vacuum-assisted immobilization system. METHODS: A retrospective review was performed of 15 consecutive cases treated with multisession GKRS. Radiosurgical targets included 12 meningiomas, 1 nonfunctioning pituitary adenoma, 1 growth hormone-secreting pituitary adenoma, and 1 pilocytic astrocytoma. GKRS was delivered in 3-5 sessions to a mean tumor volume of 8.55 mL (median, 7.3 mL; range, 1.24-22.7 mL) with a mean margin dose of 19.7 Gy (median, 20 Gy; range, 15-25 Gy). The optic nerves, chiasm, and tracts received mean doses of 3.5 Gy (range, 0.7-5.7 Gy), 3.1 Gy (range, 1-4.4 Gy), and 2.6 Gy (range, 0.83-5.45 Gy) per session. Mean biologic equivalent dose (α/ß = 2.5) was 60.9 Gy (median, 60 Gy; range, 45-79.8 Gy). Follow-up examinations were performed at 3- to 6-month intervals. RESULTS: Mean follow-up was 17.7 months (median, 13.8 months; range, 4-44.3 months), and tumor control was noted in all patients, with regression in 5 patients and stability in 10 patients. New neurologic deficits developed in 3 patients after treatment, but none of these deficits were permanent. Resection was performed in 1 patient with expressive aphasia with worsening of peritumoral T2 signal but a stable tumor on follow-up magnetic resonance imaging. The other 2 patients were managed conservatively for minor complications (ptosis, taste dysfunction), and their symptoms resolved. No patients developed deterioration in vision during the follow-up period. CONCLUSIONS: Preliminary experience with multisession GKRS appears promising, with reasonable tumor control and complication rates. Multisession stereotactic radiosurgery may expand the treatment envelope for intracranial pathologies, including targets with larger volumes and locations in close proximity to radiosensitive structures.

Gamma knife surgery for skull base meningiomas.

OBJECT: Skull base meningiomas are challenging tumors owing in part to their close proximity to important neurovascular structures. Complete microsurgical resection can be associated with significant morbidity, and recurrence rates are not inconsequential. In this study, the authors evaluate the outcomes of skull base meningiomas treated with Gamma Knife surgery (GKS) both as an adjunct to microsurgery and as a primary treatment modality. METHODS: The authors performed a retrospective review of a prospectively compiled database detailing the outcomes in 255 patients with skull base meningiomas treated at the University of Virginia from 1989 to 2006. All patients had a minimum follow-up of 24 months. The group comprised 54 male and 201 female patients, with a median age of 55 years (range 19-85 years). One hundred nine patients were treated with upfront radiosurgery, and 146 patients were treated with GKS following resection. Patients were assessed clinically and radiographically at routine intervals following GKS. Factors predictive of new neurological deficit following GKS were assessed via univariate and multivariate analysis, and Kaplan-Meier analysis and Cox multivariate regression analysis were used to assess factors predictive of tumor progression. RESULTS: Meningiomas were centered over the cerebellopontine angle in 43 patients (17%), the clivus in 40 (16%), the petroclival region in 28 (11%), the petrous region in 6 (2%), and the parasellar region in 138 (54%). The median duration of follow-up was 6.5 years (range 2-18 years). The mean preradiosurgery tumor volume was 5.0 cm(3) (range 0.3-54.8 cm(3)). At most recent follow-up, 220 patients (86%) displayed either no change or a decrease in tumor volume, and 35 (14%) displayed an increase in volume. Actuarial progression-free survival at 3, 5, and 10 years was 99%, 96%, and 79%, respectively. In Cox multivariate analysis, pre-GKS covariates associated with tumor progression included age greater then 65 years (HR 3.41, 95% CI 1.63-7.13, p = 0.001) and decreasing dose to tumor margin (HR 0.90, 95% CI 0.80-1.00, p = 0.05). At most recent clinical follow-up, 230 patients (90%) demonstrated no change or improvement in their neurological condition and the condition of 25 patients had deteriorated (10%). In multivariate analysis, the factors predictive of new or worsening symptoms were increasing duration of follow-up (OR 1.01, 95% CI 1.00-1.02, p = 0.015), tumor progression (OR 2.91, 95% CI 1.60-5.31, p < 0.001), decreasing maximum dose (OR 0.90, 95% CI 0.84-0.97, p = 0.007), and petrous or clival location versus parasellar, petroclival, and cerebellopontine angle location (OR 3.47, 95% CI 1.23-9.74, p = 0.018). CONCLUSIONS: Stereotactic radiosurgery offers a high rate of tumor control and neurological preservation in patients with skull base meningiomas. After radiosurgery, better outcomes were observed for those receiving an optimal radiosurgery dose and harboring tumors located in a cerebellopontine angle, parasellar, or petroclival location.

Gamma Knife surgery of meningiomas located in the posterior fossa: factors predictive of outcome and remission.

OBJECT: Although numerous studies have analyzed the role of stereotactic radiosurgery for intracranial meningiomas, few studies have assessed outcomes of posterior fossa meningiomas after stereotactic radiosurgery. In this study, the authors evaluate the outcomes of posterior fossa meningiomas treated with Gamma Knife surgery (GKS). The authors also assess factors predictive of new postoperative neurological deficits and tumor progression. METHODS: A retrospective review was performed of a prospectively compiled database documenting the outcomes of 152 patients with posterior fossa meningiomas treated at the University of Virginia from 1990 to 2006. All patients had a minimum follow-up of 24 months. There were 30 males and 122 females, with a median age of 58 years (range 12-82 years). Seventy-five patients were treated with radiosurgery initially, and 77 patients were treated with GKS after resection. Patients were assessed clinically and radiographically at routine intervals following GKS. Factors predictive of new neurological deficit following GKS were assessed via univariate and multivariate analysis, and Kaplan-Meier analysis and Cox multivariate regression analysis were used to assess factors predictive of tumor progression. RESULTS: Patients had meningiomas centered over the tentorium (35 patients, 23%), cerebellopontine angle (43 patients, 28%), petroclival region (28 patients, 18%), petrous region (6 patients, 4%), and clivus (40 patients, 26%). The median follow-up was 7 years (range 2-16 years). The mean preradiosurgical tumor volume was 5.7 cm(3) (range 0.3-33 cm(3)), and mean postradiosurgical tumor volume was 4.9 cm(3) (range 0.1-33 cm(3)). At last follow-up, 55 patients (36%) displayed no change in tumor volume, 78 (51%) displayed a decrease in volume, and 19 (13%) displayed an increase in volume. Kaplan-Meier analysis demonstrated radiographic progression-free survival at 3, 5, and 10 years to be 98%, 96%, and 78%, respectively. In Cox multivariable analysis, pre-GKS covariates associated with tumor progression included age greater than 65 years (hazard ratio [HR] 3.24, 95% CI 1.12-9.37; p = 0.03) and a low dose to the tumor margin (HR 0.76, 95% CI 0.60-0.97; p = 0.03), and post-GKS covariates included shunt-dependent hydrocephalus (HR 25.0, 95% CI 3.72-100.0; p = 0.001). At last clinical follow-up, 139 patients (91%) demonstrated no change or improvement in their neurological condition, and 13 patients showed symptom deterioration (9%). In multivariate analysis, the only factors predictive of new or worsening symptoms were clival or petrous location (OR 4.0, 95% CI 1.1-13.7; p = 0.03). CONCLUSIONS: Gamma Knife surgery offers an acceptable rate of tumor control for posterior fossa meningiomas and accomplishes this with a low incidence of neurological deficits. In patients selected for GKS, tumor progression is associated with age greater than 65 years and decreasing dose to the tumor margin. Clival- or petrous-based locations are predictive of an increased risk of new or worsening neurological deficit following GKS.

Gamma knife radiosurgery of tentorial meningiomas.

OBJECTIVE: Tentorial meningiomas are complex lesions that may not always be completely resected without significant morbidity or mortality. In this study, we evaluate the outcomes of tentorial meningiomas treated with Gamma Knife radiosurgery (GKRS). METHODS: We performed a retrospective review of a prospectively compiled database evaluating the outcomes of 35 patients with tentorial meningiomas treated at the University of Virginia from 1990 to 2006. There were 29 females and 6 males with a median age of 60 years (range 21-82). Twenty were treated with primary radiosurgery, and 15 patients were treated with adjuvant radiosurgery after surgical resection. Patients were assessed clinically and radiologically at routine intervals following GKRS. Kaplan-Meier analysis was used to assess tumor progression. RESULTS: The mean follow-up was 5 years (range 2-16 years). The mean pre-radiosurgery tumor volume was 5.1 cc (range 0.7-27.3cc). At last follow-up, 31 patients (89%) displayed either no growth or a decrease in tumor volume. Four (11%) patients displayed an increase in volume. Kaplan Meier analysis demonstrated radiographic progression free survival at 3, 5, and 10 years to be 96%, 91%, and 73% respectively. At the last clinical follow-up, 33 patients (94%) demonstrated no change or improvement in their neurological condition and 2 patients clinically declined (6%). CONCLUSION: GKRS offers an acceptable rate of tumor control for tentorial meningiomas, and accomplishes this with a low incidence of new or worsening neurological deficits.

Gamma Knife surgery for arteriovenous malformations in children.

OBJECT: The aim of this study was to evaluate the long-term imaging and clinical outcomes of intracranial arteriovenous malformations (AVMs) in children treated with Gamma Knife surgery (GKS). METHODS: Between 1989 and 2007, 200 patients with AVMs who were 18 years of age or younger were treated at the University of Virginia Health System. Excluding 14 patients who had not reached 2-year follow-up, 186 patients comprised this study. Hemorrhage was the most common presenting symptom leading to the diagnosis of AVMs (71.5%). The mean nidus volume was 3.2 cm(3) at the time of GKS, and a mean prescription dose of 21.9 Gy was used. RESULTS: After initial GKS, 49.5% of patients achieved total angiographic obliteration. Forty-one patients whose AVM nidi remained patent underwent additional GKS. The obliteration rate increased to 58.6% after a second or multiple GKS. Subtotal obliteration was achieved in 9 patients (4.8%). Forty-nine patients (26.3%) still had a patent residual nidus. In 19 patients (10.2%), obliteration was confirmed on MR imaging only. Ten patients had 17 hemorrhages during the follow-up period. The hemorrhage rate was 5.4% within 2 years after GKS and 0.8% between 2 and 5 years. Six patients developed neurological deficits along with the radiation-induced changes. Two patients developed asymptomatic meningiomas 10 and 12 years after GKS. After a mean clinical follow-up of 98 months, less than 4% of patients had difficulty attending school or developing a career. CONCLUSIONS: Gamma Knife surgery offers a reasonable chance of obliteration of an AVM in pediatric patients. The incidence of symptomatic radiation-induced changes is relatively low; however, long-term clinical and imaging follow-up is required to identify delayed cyst formation and secondary tumors.

Gamma knife radiosurgery of meningiomas involving the foramen magnum.

BACKGROUND: Foramen magnum meningiomas represent a challenging clinical entity. Although resection is performed for those with a mass effect, complete resection is not always feasible. For some patients, stereotactic radiosurgery may be used as the primary treatment modality. We evaluatedthe long-term outcome of Gamma Knife radiosurgery (GKRS) for the treatment of patientswith a foramen magnum meningioma. MATERIALS AND METHODS: Between 1991 and 2005, 222 patients with a meningioma in the posterior fossa were treated with GKRS at the University of Virginia. Of these patients, 5 had meningiomas involving the foramen magnum. At the time of GKRS, the median age of the patients was 60 years (range, 51-78). Three patients were treated with radiosurgery following an initial resection and 2 were treated with upfront radiosurgery. The patients were assessed clinically and radiologically at routine intervals following GKRS. RESULTS: The median tumor volume was 6.8 cc (range 1.9-17 cc). The GKRS tumor received a marginal dose of 12 Gy (range 10-15), and the median number of isocenters was 5 (range 3-19). The mean follow-up was 6 years (range 4-13). One lesion increased in size following GKRS requiring a second treatment, resulting in size stabilization. At the time of the last follow-up, all meningiomas had either demonstrated no growth (n = 4) or reduction in size (n = 1). No patients experienced post-radiotherapy complications. CONCLUSIONS: GKRS affords a high rate of tumor control and preservation of neurologic function for patients with foramen magnum meningiomas. Further study of its role in the neurosurgical management of such patients seems warranted.

Treatment of glomus jugulare tumors with gamma knife radiosurgery.

OBJECTIVE: Surgical resection, preoperative embolization, radiation therapy, and stereotactic radiosurgery have been used to treat glomus jugulare tumors (GJT). However, the optimal treatment of these tumors remains unclear. The authors report their data on treatment of GJTs with gamma knife radiosurgery (GKS). DESIGN: Retrospective review and pooled analysis. METHODS: Fifteen patients (nine female, six male) were treated with GKS at a single tertiary care institution for GJTs over a 14-year period. Criteria for selection included GKS followed by at least one posttreatment radiographic image, and volumetric analysis was performed. A required 15% change in tumor volume was considered real. Pooled analysis was performed to compare outcomes with other series. RESULTS: The mean total radiologic follow-up was 43.2 months. The mean dose-to-the tumor margin was 14.6 Gy. The mean tumor size at treatment was 7.3 cc and 6.3 cc at last follow-up. After treatment, seven tumors decreased (46.7%), five remained unchanged (33.3%), and three (20%) grew on imaging. Treatment failures received a mean marginal dose of 13.2 Gy compared with 15.1 Gy for treatment successes (P =.08). Overall tumor control rate after GKS in the existing literature with inclusion of the present study is 90.5%. CONCLUSIONS: GKS is an effective treatment option for patients with GJTs, including those with prior surgical resection. Marginal radiation doses greater than 13 Gy may be optimal for tumor control. Longer follow-up will better define the benefits and risks of stereotactic radiosurgery in treating patients with GJT.