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Leopold Arko IV, Eric Quach, Vincent Nguyen, Daniel Chang, Vishad Sukul and Bong-Soo Kim

Object

Spinal epidural abscess (SEA) is a rare condition that has previously been treated with urgent surgical decompression and antibiotics. Recent availability of MRI makes early diagnosis possible and allows for the nonoperative treatment of SEA in select patients. The first retrospective review of medically and surgically managed SEA was published in 1999, and since that time several other retrospective institutional reports have been published. This study reviews these published reports and compares pooled data with historical treatment data.

Methods

A PubMed keyword and Boolean search using (“spinal epidural abscess” OR “spinal epidural abscesses” AND [management OR treatment]) returned 429 results. Filters for the English language and publications after 1999 were applied, as the first study comparing operative and nonoperative management was published that year. Articles comparing operative to nonoperative treatment strategies for SEA were identified, and the references were further reviewed for additional articles. Studies involving at least 10 adult patients (older than 18 years) were included. Case reports, studies reporting either medical or surgical management only, studies not reporting indications for conservative management, or studies examining SEA as a result of a specific pathogen were excluded.

Results

Twelve articles directly comparing surgical to nonsurgical management of SEA were obtained. These articles reported on a total of 1099 patients. The average age of treated patients was 57.24 years, and 62.5% of treated patients were male. The most common pathogens found in blood and wound cultures were Staphylococcus aureus (63.6%) and Streptococcus species (6.8%). The initial treatment was surgery in 59.7% of cases and medical therapy in 40.3%. This represented a significant increase in the proportion of medically managed patients in comparison with the historical control prior to 1999 (p < 0.05). Patients with no neurological deficits were significantly more likely to be treated medically than surgically (p < 0.05). There was no statistically significant difference overall between surgical and nonsurgical management, although several risk factors may predict failure of medical management.

Conclusions

. Since the first reports of nonoperative treatment of SEA, there has been a substantial trend toward treating neurologically intact patients with medical management. Nevertheless, medical therapy fails in a fair number of cases involving patients with specific risk factors, and patients with these risk factors should be closely observed in consideration for surgery. Further research may help identify patients at greater risk for failure of medical therapy.

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Kelly Lamiman, Kenneth K. Wong, Benita Tamrazi, Jason D. Nosrati, Arthur Olch, Eric L. Chang and Erin N. Kiehna

OBJECTIVE

When complete resection of craniopharyngioma is not achievable or the sequelae are prohibitive, limited surgery and radiation therapy have demonstrated excellent local disease control while minimizing treatment-related sequelae. When residual tissue exists, there is a propensity for further cyst development and expansion during and after radiation therapy. This can result in obstructive hydrocephalus, visual changes, and/or clinical decline. The authors present a quantitative analysis of cyst expansion during and after radiotherapy and examine how it affected subsequent management.

METHODS

The authors performed an institutional review board–approved retrospective study of patients with histologically confirmed craniopharyngioma treated between 2000 and 2015 with surgery and intensity-modulated radiation therapy (IMRT) at a single institution. Volumetric measurements of cyst contours were generated by radiation oncology treatment planning software postoperatively, during IMRT, and up to 12 months after IMRT. Patient, tumor, and treatment–related variables were collected until the last known follow-up and were analyzed.

RESULTS

Twenty-seven patients underwent surgery and IMRT. The median total radiation dose was 54 Gy. Of the 27 patients, 11 patients (40.7%) demonstrated cyst expansions within 1 year of IMRT. Of note, all tumors with cyst expansion were radiographically Puget Grade 2. Maximal cyst expansion peaked at 4.27 months following radiation therapy, with a median volume growth of 4.1 cm3 (mean 9.61 cm3) above the postoperative cyst volume. Eight patients experienced spontaneous cyst regression without therapeutic intervention. Three patients experienced MRI-confirmed cyst enlargement during IMRT, all of whom required adaptive planning to ensure adequate coverage of the entire tumor volume. Two of these 3 patients required ventriculoperitoneal shunt placement and additional intervention. One underwent additional resection, and the other had placement of an intracystic catheter for aspiration and delivery of intracystic interferon within 12 months of completing IMRT. All 3 patients now have stable disease.

CONCLUSIONS

Craniopharyngioma cyst expansion occurred in approximately 40% of the patients during or after radiotherapy. In the majority of patients, cyst expansion was a self-limiting process and did not confer a worse outcome. During radiotherapy, cyst expansion may be apparent on image-guided radiation therapy. Adaptive IMRT planning may be required to ensure that the intended IMRT dose covers the entire tumor and cyst volume. The sequelae of cyst expansion include progressive hydrocephalus, which may be treated with a shunt. For patients with solitary cyst expansion, cyst aspiration and/or intracystic interferon may result in disease control.

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Shervin R. Dashti, Humain Baharvahdat, Robert F. Spetzler, Eric Sauvageau, Steven W. Chang, Michael F. Stiefel, Min S. Park and Nicholas C. Bambakidis

Object

Postoperative infection after cranial surgery is a serious complication that requires immediate recognition and treatment. In certain cases such as postoperative meningitis, the patient can be treated with antibiotics only. In cases that involve a bone flap infection, subdural empyema, or cerebral abscess, however, reoperation is often needed. There has been significant disagreement regarding the incidence of postoperative central nervous system (CNS) infections following cranial surgery. In this paper the authors' goal was to perform a retrospective review of the incidence of CNS infection after cranial surgery at their institution. They focused their review on those patients who required repeated surgery to treat the infection.

Methods

The authors reviewed the medical records and imaging studies in all patients who underwent a craniotomy or stereotactic drainage for CNS infection over the past 10 years. Subgroup analysis was then performed in patients whose infection was a result of a previous cranial operation to determine the incidence, factors associated with infection, and the type of infectious organism. Patients treated nonoperatively (that is, those who received intravenous antibiotics for postoperative meningitis or cellulitis) were not included. Patients treated for wound infection without intracranial pus were also not included.

Results

During the study period from January 1997 through December 2007, ~ 16,540 cranial surgeries were performed by 25 neurosurgeons. These included elective as well as emergency and trauma cases. Of these cases 82 (0.5%) were performed to treat postoperative infection in 50 patients. All 50 patients underwent their original surgery at the authors' institution. The median age was 51 years (range 2–74 years). There were 26 male and 24 female patients.

The most common offending organism was methicillin-sensitive Staphylococcus aureus, which was found in 10 of 50 patients. Gram-negative rods were found in 15 patients. Multiple organisms were identified in specimens obtained in 5 patients. Six patients had negative cultures. Most craniotomies leading to subsequent infection were performed for tumors or other mass lesions (23 of 50 patients), followed by craniotomies for hemorrhage and vascular lesions. Almost half of the patients underwent > 1 cranial operation before presenting with infection.

Conclusions

Postoperative infection after cranial surgery is an important phenomenon that needs immediate recognition. Even with strict adherence to sterile techniques and administration of antibiotic prophylaxis, a small percentage of these patients will develop an infection severe enough to require reoperation.

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Eric W. Franz, J. Nicole Bentley, Patricia P. S. Yee, Kate W. C. Chang, Jennifer Kendall-Thomas, Paul Park and Lynda J. S. Yang

OBJECT

Patient outcome measures are becoming increasingly important in the evaluation of health care quality and physician performance. Of the many novel measures currently being explored, patient satisfaction and other subjective measures of patient experience are among the most heavily weighted. However, these subjective measures are strongly influenced by a number of factors, including patient demographics, level of understanding of the disorder and its treatment, and patient expectations. In the present study, patients referred to a neurosurgery clinic for degenerative spinal disorders were surveyed to determine their understanding of lumbar spondylosis diagnosis and treatment.

METHODS

A multiple-choice, 6-question survey was distributed to all patients referred to a general neurosurgical spine clinic at a tertiary care center over a period of 11 months as a quality improvement initiative to assist the provider with individualized patient counseling. The survey consisted of questions designed to assess patient understanding of the role of radiological imaging in the diagnosis and treatment of low-back and leg pain, and patient perception of the indications for surgical compared with conservative management. Demographic data were also collected.

RESULTS

A total of 121 surveys were included in the analysis. More than 50% of the patients indicated that they would undergo spine surgery based on abnormalities found on MRI, even without symptoms; more than 40% of patients indicated the same for plain radiographs. Similarly, a large proportion of patients (33%) believed that back surgery was more effective than physical therapy in the treatment of back pain without leg pain. Nearly one-fifth of the survey group (17%) also believed that back injections were riskier than back surgery. There were no significant differences in survey responses among patients with a previous history of spine surgery compared with those without previous spine surgery.

CONCLUSIONS

These results show that a surprisingly high percentage of patients have misconceptions regarding the diagnosis and treatment of lumbar spondylosis, and that these misconceptions persist in patients with a history of spine surgery. Specifically, patients overemphasize the value of radiological studies and have mixed perceptions of the relative risk and effectiveness of surgical intervention compared with more conservative management. These misconceptions have the potential to alter patient expectations and decrease satisfaction, which could negatively impact patient outcomes and subjective valuations of physician performance. While these results are preliminary, they highlight a need for improved communication and patient education during surgical consultation for lumbar spondylosis.

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Shervin R. Dashti, Humain Baharvahdat, Eric Sauvageau, Steven W. Chang, Michael F. Stiefel, Min S. Park, Robert F. Spetzler and Nicholas C. Bambakidis

✓ Brain abscess is a rare but very dangerous neurosurgical lesion. Prompt diagnosis and emergency surgical evacuation are the hallmarks of therapy. Brain abscess following ischemic and hemorrhagic stroke is a rare entity. These cases are often preceded by episodes of bacteremia, sepsis, and local infection. The authors report the case of a 30-year-old woman who presented with a cerebral abscess at the site of a recent intraparenchymal hemorrhage.

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Skeletal dysplasia involving the subaxial cervical spine

Report of two cases and review of the literature

Gregory P. Lekovic, Nitin R. Mariwalla, Eric M. Horn, Steven Chang, Harold L. Rekate and Nicholas Theodore

✓ Because skeletal dysplasias are primary disorders of bone, they have not been commonly understood as neurosurgical diseases. Nevertheless, neurosurgical complications are commonly encountered in many cases of dysplasia syndromes. The authors present two cases of skeletal dysplasia that caused overt instability of the cervical spine. One patient with a diagnosis of Gorham disease of the cervical spine was treated with prolonged fixation in a halo brace after an initial attempt at instrumentation with a posterior occiput–C4 fusion. The other patient, who at birth was identified to have camptomelic dysplasia, has been treated conservatively from the outset. Although these two patients presented with different disorders—in one patient adequate mature bone never formed and in the other patient progressive bone loss became apparent after a seemingly normal initial development—these cases demonstrate unequivocally that surgical options for fusion are ultimately limited by the quality of the underlying bone. In patients in whom the bone itself is inadequate for use as a substrate for fusion, there are currently limited treatment options. Future improvements in our understanding of chondrogenesis and ossification may lead to the design of superior methods of encouraging fusion in these patients; however, at the present time, long-term maintenance in a halo brace may, in fact, be the only treatment.

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Nathan T. Zwagerman, Eric W. Wang, Samuel S. Shin, Yue-Fang Chang, Juan C. Fernandez-Miranda, Carl H. Snyderman and Paul A. Gardner

OBJECTIVE

Based on a null hypothesis that the use of short-term lumbar drainage (LD) after endoscopic endonasal surgery (EES) for intradural pathology does not prevent postoperative CSF leaks, a trial was conducted to assess the effect of postoperative LD on postoperative CSF leak following standard reconstruction.

METHODS

A prospective, randomized controlled trial of lumbar drain placement after endoscopic endonasal skull base surgery was performed from February 2011 to March 2015. All patients had 3-month follow-up data. Surgeons were blinded to which patients would or would not receive the drain until after closure was completed. An a priori power analysis calculation assuming 80% of power, 5% postoperative CSF leak rate in the no-LD group, and 16% in the LD group determined a planned sample size of 186 patients. A routine data and safety check was performed with every 50 patients being recruited to ensure the efficacy of randomization and safety. These interim tests were run by a statistician who was not blinded to the arms they were evaluating. This study accrued 230 consecutive adult patients with skull base pathology who were eligible for endoscopic endonasal resection. Inclusion criteria (high-flow leak) were dural defect greater than 1 cm2 (mandatory), extensive arachnoid dissection, and/or dissection into a ventricle or cistern. Sixty patients were excluded because they did not meet the inclusion criteria. One hundred seventy patients were randomized to either receive or not receive a lumbar drain.

RESULTS

One hundred seventy patients were randomized, with a mean age of 51.6 years (range 19–86 years) and 38% were male. The mean BMI for the entire cohort was 28.1 kg/m2. The experimental cohort with postoperative LD had an 8.2% rate of CSF leak compared to a 21.2% rate in the control group (odds ratio 3.0, 95% confidence interval 1.2–7.6, p = 0.017). In 106 patients in whom defect size was measured intraoperatively, a larger defect was associated with postoperative CSF leak (6.2 vs 2.9 cm2, p = 0.03). No significant difference was identified in BMI between those with (mean 28.4 ± 4.3 kg/m2) and without (mean 28.1 ± 5.6 kg/m2) postoperative CSF leak (p = 0.79). Furthermore, when patients were grouped based on BMI < 25, 25–29.9, and > 30 kg/m2, no difference was noted in the rates of CSF fistula (p = 0.97).

CONCLUSIONS

Among patients undergoing intradural EES judged to be at high risk for CSF leak as defined by the study’s inclusion criteria, perioperative LD used in the context of vascularized nasoseptal flap closure significantly reduced the rate of postoperative CSF leaks.

Clinical trial registration no.: NCT03163134 (clinicaltrials.gov).

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Nicholas S. Boehling, David R. Grosshans, Pamela K. Allen, Mary F. McAleer, Allen W. Burton, Syed Azeem, Laurence D. Rhines and Eric L. Chang

Object

The aim of this study was to identify potential risk factors for and determine the rate of vertebral compression fracture (VCF) after intensity-modulated, near-simultaneous, CT image–guided stereotactic body radiotherapy (SBRT) for spinal metastases.

Methods

The study group consisted of 123 vertebral bodies (VBs) in 93 patients enrolled in prospective protocols for metastatic disease. Data from these patients were retrospectively analyzed. Stereotactic body radiotherapy consisted of 1, 3, or 5 fractions for overall median doses of 18, 27, and 30 Gy, respectively. Magnetic resonance imaging studies, obtained at baseline and at each follow-up, were evaluated for VCFs, tumor involvement, and radiographic progression. Self-reported average pain levels were scored based on the 11-point (0–10) Brief Pain Inventory both at baseline and at follow-up. Obesity was defined as a body mass index ≥ 30.

Results

The median imaging follow-up was 14.9 months (range 1–71 months). Twenty-five new or progressing fractures (20%) were identified, and the median time to progression was 3 months after SBRT. The most common histologies included renal cancer (36 VBs, 10 fractures, 10 tumor progressions), breast cancer (20 VBs, 0 fractures, 5 tumor progressions), thyroid cancer (14 VBs, 1 fracture, 2 tumor progressions), non–small cell lung cancer (13 VBs, 3 fractures, 3 tumor progressions), and sarcoma (9 VBs, 2 fractures, 2 tumor progressions). Fifteen VBs were treated with kyphoplasty or vertebroplasty after SBRT, with 5 procedures done for preexisting VCFs. Tumor progression was noted in 32 locations (26%) with 5 months' median time to progression. At the time of noted fracture progression there was a trend toward higher average pain scores but no significant change in the median value. Univariate logistic regression showed that an age > 55 years (HR 6.05, 95% CI 2.1–17.47), a preexisting fracture (HR 5.05, 95% CI 1.94–13.16), baseline pain and narcotic use before SBRT (pain: HR 1.31, 95% CI 1.06–1.62; narcotic: HR 2.98, 95% CI 1.17–7.56) and after SBRT (pain: HR 1.34, 95% CI 1.06–1.70; narcotic: HR 3.63, 95% CI 1.41–9.29) were statistically significant predictors of fracture progression. On multivariate analysis an age > 55 years (HR 10.66, 95% CI 2.81–40.36), a preexisting fracture (HR 9.17, 95% CI 2.31–36.43), and baseline pain (HR 1.41, 95% CI 1.05–1.9) were found to be significant risks, whereas obesity (HR 0.02, 95% CI 0–0.2) was protective.

Conclusions

Stereotactic body radiotherapy is associated with a significant risk (20%) of VCF. Risk factors for VCF include an age > 55 years, a preexisting fracture, and baseline pain. These risk factors may aid in the selection of which spinal SBRT patients should be considered for prophylactic vertebral stabilization or augmentation procedures. Clinical trial registration no.: NCT00508443.

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Kevin Diao, Shelly X. Bian, David M. Routman, Cheng Yu, Paul E. Kim, Naveed A. Wagle, Michael K. Wong, Gabriel Zada and Eric L. Chang

OBJECTIVE

Tumor and edema volume changes of brain metastases after stereotactic radiosurgery (SRS) and ipilimumab are not well described, and there is concern regarding the safety of combination treatment. The authors evaluated tumor, edema, and adverse radiation-induced changes after SRS with and without ipilimumab and identified associated risk factors.

METHODS

This single-institution retrospective study included 72 patients with melanoma brain metastases treated consecutively with upfront SRS from 2006 to 2015. Concurrent ipilimumab was defined as ipilimumab treatment within 4 weeks of SRS. At baseline and during each follow-up, tumor and edema were measured in 3 orthogonal planes. The (length × width × height/2) formula was used to estimate tumor and edema volumes and was validated in the present study for estimation of edema volume. Tumor and edema volume changes from baseline were compared using the Kruskal-Wallis test. Local failure, lesion hemorrhage, and treatment-related imaging changes (TRICs) were analyzed with the Cox proportional hazards model.

RESULTS

Of 310 analyzed lesions, 91 were not treated with ipilimumab, 59 were treated with concurrent ipilimumab, and 160 were treated with nonconcurrent ipilimumab. Of 106 randomly selected lesions with measurable peritumoral edema, the mean edema volume by manual contouring was 7.45 cm3 and the mean volume by (length × width × height)/2 formula estimation was 7.79 cm3 with R2 = 0.99 and slope of 1.08 on line of best fit. At 6 months after SRS, the ipilimumab groups had greater tumor (p = 0.001) and edema (p = 0.005) volume reduction than the control group. The concurrent ipilimumab group had the highest rate of lesion response and lowest rate of lesion progression (p = 0.002). Within the concurrent ipilimumab group, SRS dose ≥ 20 Gy was associated with significantly greater median tumor volume reduction at 3 months (p = 0.01) and 6 months (p = 0.02). The concurrent ipilimumab group also had the highest rate of lesion hemorrhage (p = 0.01). Any ipilimumab was associated with higher incidence of symptomatic TRICs (p = 0.005). The overall incidence of pathologically confirmed radiation necrosis (RN) was 2%. In multivariate analysis, tumor and edema response at 3 months were the strongest predictors of local failure (HR 0.131 and HR 0.125) and lesion hemorrhage (HR 0.225 and HR 0.262). Tumor and edema response at 1.5 months were the strongest predictors of TRICs (HR 0.144 and HR 0.297).

CONCLUSIONS

The addition of ipilimumab improved tumor and edema volume reduction but was associated with a higher incidence of lesion hemorrhage and symptomatic TRICs. There may be a radiation dose-response relationship between SRS and ipilimumab when administered concurrently. Early tumor and edema response were excellent predictors of subsequent local failure, lesion hemorrhage, and TRICs. The incidence of pathologically proven RN was low, supporting the relative safety of ipilimumab in radiosurgery treatment.

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Jonathan N. Sellin, William Reichardt, Andrew J. Bishop, Dima Suki, Laurence D. Rhines, Stephen H. Settle, Paul D. Brown, Jing Li, Ganesh Rao, Eric L. Chang and Claudio E. Tatsui

OBJECT

Palliative resection of renal cell carcinoma (RCC) spinal metastasis is indicated in cases of neurological compromise or mechanical instability, whereas conventional external beam radiotherapy (EBRT) is commonly used for pain control. Recently, spinal stereotactic radiosurgery (SRS) has emerged as a safe alternative, delivering higher therapeutic doses of radiation to spinal metastases. To better understand factors affecting survival in patients undergoing spinal SRS for metastatic RCC, the authors performed a retrospective analysis of a consecutive series of cases at a tertiary cancer center.

METHODS

Patients harboring contiguous sites of vertebral body involvement from metastatic RCC who received upfront spinal SRS treatment at The University of Texas MD Anderson Cancer Center between 2005 and 2012 were identified. Demographic data, pain scores, radiographic data, overall survival, complications, status of systemic disease, neurological and functional status, and time between primary diagnosis and diagnosis of metastasis (systemic and spinal) were analyzed to determine their influence on survival.

RESULTS

Thirty-seven patients receiving treatment for 40 distinct, contiguous sites of disease were included. The median overall survival after spinal SRS was 16.3 months (range 7.4–25.3 months). Univariate analysis revealed several factors significantly associated with improved overall survival. Local progression after spinal SRS was associated with worse overall survival compared with sustained local control (HR 3.4, 95% CI 1.6–7.4, p = 0.002). Median survival in patients with a Karnofsky Performance Scale (KPS) score ≥ 70 was longer than in patients with a KPS score < 70 (HR 4.7, 95% CI 2.1–10.7, p < 0.001). Patients with neurological deficits at the time of spinal SRS had a shorter median survival than those without (HR 4.2, 95% CI 1.4–12.0, p = 0.008). Individuals with nonprogressive systemic disease at the time of spinal SRS had a longer median survival than those with systemic progression at the time of treatment (HR 8.3, 95% CI 3.3–20.7, p < 0.001). Median survival in patients experiencing any metastasis < 12 months after primary RCC diagnosis was shorter than in patients experiencing any metastasis > 12 months after primary diagnosis, a difference that approached but did not attain significance (HR 1.9, 95% CI 0.90–4.1, p = 0.09). On multivariate analysis, local progression of disease after spinal SRS, metastasis < 12 months after primary, KPS score ≤ 70, and progression of systemic disease at time of spinal SRS all remained significant factors influencing survival (respectively, HR 3.7, p = 0.002; HR 2.6, p = 0.026; HR 4.0, p = 0.002; and HR 13.2, p < 0.001).

CONCLUSIONS

We identified several factors associated with survival after spinal SRS for RCC metastases, including local progression, time between first metastasis and primary RCC diagnosis, KPS score, presence of neurological deficits, and progressive metastatic disease. These factors should be taken into consideration when considering a patient for spinal SRS for RCC metastases.