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Jason P. Sheehan, Zhiyuan Xu, David J. Salvetti, Paul J. Schmitt and Mary Lee Vance

Object

Cushing's disease is a challenging neuroendocrine disorder. Although resection remains the primary treatment option for most patients, the disease persists if there is residual or recurrent tumor. Stereotactic radiosurgery has been used to treat patients with persistent Cushing's disease after a prior resection. The authors report on the long-term risks and benefits of radiosurgery for Cushing's disease.

Methods

A retrospective review of a prospectively collected database of radiosurgery patients was undertaken at the University of Virginia. All patients with Cushing's disease treated with Gamma Knife surgery (GKS) were identified. Those without at least 12 months of clinical and radiological follow-up were excluded from this analysis. Rates of endocrine remission, tumor control, and adverse events were assessed. Statistical methods were used to identify favorable and unfavorable prognostic factors.

Results

Ninety-six patients with the required follow-up data were identified. The mean tumor margin dose was 22 Gy. The median follow-up was 48 months (range 12–209.8 months). At the last follow-up, remission of Cushing's disease occurred in 70% of patients. The median time to remission among all patients was 16.6 months (range 1–165.7 months). The median time to remission in those who had temporarily stopped taking ketoconazole at the time of GKS was 12.6 months, whereas it was 21.8 months in those who continued to receive ketoconazole (p < 0.012). Tumor control was achieved in 98% of patients. New loss of pituitary function occurred in 36% of patients. New or worsening cranial neuropathies developed in 5 patients after GKS, with the most common involving cranial nerves II and III.

Conclusions

Gamma Knife surgery offers a high rate of tumor control and a reasonable rate of endocrine remission in patients with Cushing's disease. The cessation of cortisol-lowering medications around the time of GKS appears to result in a more rapid rate of remission. Delayed hypopituitarism and endocrine recurrence develop in a minority of patients and underscore the need for long-term multidisciplinary follow-up.

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Brian J. Williams, Zhiyuan Xu, David J. Salvetti, Ian T. McNeill, James Larner and Jason P. Sheehan

Object

Gamma Knife surgery (GKS) is a safe and effective treatment for patients with small to moderately sized vestibular schwannomas (VSs). Reports of stereotactic radiosurgery for large VSs have demonstrated worse tumor control and preservation of neurological function. The authors endeavored to assess the effect of size of VSs treated using GKS.

Methods

This study was a retrospective comparison of 24 patients with large VSs (> 3 cm in maximum diameter) treated with GKS compared with 49 small VSs (≤ 3 cm) matched for age, sex, radiosurgical margin and maximal doses, length of follow-up, and indication.

Results

Actuarial tumor progression-free survival (PFS) for the large VS cohort was 95.2% and 81.8% at 3 and 5 years, respectively, compared with 97% and 90% for small VSs (p = 0.009). Overall clinical outcome was better in small VSs compared with large VSs (p < 0.001). Patients with small VSs presenting with House-Brackmann Grade I (good facial function) had better neurological outcomes compared with patients with large VSs (p = 0.003). Treatment failure occurred in 6 patients with large VSs; 3 each were treated with resection or repeat GKS. Treatment failure did not occur in the small VS group. Two patients in the large VS group required ventriculoperitoneal shunt placement. Univariate analysis did not identify any predictors of treatment failure among the large VS cohort.

Conclusions

Patients with large VSs treated using GKS had shorter PFS and worse clinical outcomes compared with age-, sex-, and indication-matched patients with small VSs. Nevertheless, GKS has efficacy for some patients with large VSs and represents a reasonable treatment option for selected patients.

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Gurpreet S. Gandhoke, Sabri Yilmaz, Lorelei Grunwaldt, Ronald L. Hamilton, David J. Salvetti and Stephanie Greene

While spinal epidural arteriovenous malformations, fistulas, and shunts are well reported, the presence of a venous malformation in the spinal epidural space is a rare phenomenon. Herein, the authors report the clinical presentation, imaging findings, pathological features, and the outcome of surgical and percutaneous interventional management of a mediastinal and spinal epidural venous malformation in a young woman who presented clinically with neurogenic claudication from presumed venous hypertension precipitating the formation of a syrinx. The patient underwent a C6–T5 osteoplastic laminectomy for decompression of the spinal canal and subtotal resection of the epidural venous malformation, followed by percutaneous sclerotherapy of the mediastinal and residual anterior spinal venous malformation. She developed transient loss of dorsal column sensation, which returned to baseline within 3 weeks of the surgery. A 6-month postoperative MRI study revealed complete resolution of the syrinx and the mediastinal venous malformation. Twelve months after the surgery, the patient has had resolution of all neurological symptoms with the exception of her premorbid migraine headaches. A multidisciplinary approach with partial resection and the use of percutaneous sclerotherapy for the residual malformation can be used to successfully treat a complex venous malformation.

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David J. Salvetti, Tara G. Nagaraja, Ian T. McNeill, Zhiyuan Xu and Jason Sheehan

Object

It has been generally accepted that Gamma Knife surgery (GKS) is an effective primary or adjunct treatment for patients with 1–4 metastases to the brain. The number of studies detailing the use of GKS for 5 or more brain metastases, however, remains minimal. The aim of the current retrospective study was to elucidate the utility of GKS in patients with 5–15 brain metastases.

Methods

Patients were chosen for GKS based on prior MRI of these metastatic lesions and a known primary cancer diagnosis. Magnetic resonance imaging was used post-GKS to assess tumor control; patients were also followed up clinically. Overall survival (OS) from the date of GKS was used as the primary end point. Statistical analysis was performed to identify prognostic factors related to OS.

Results

Between 2003 and 2012, 96 patients were treated for a total of 704 metastatic brain lesions. The histology of these lesions varied among non–small cell lung cancer (NSCLC), breast cancer, melanoma, renal cancer, and other more rare carcinomas. At the initial treatment, 18 of the patients (18.8%) were categorized in Recursive Partitioning Analysis (RPA) Class 1 and 77 (80.2%) in RPA Class 2; none were in RPA Class 3. The median number of treated lesions was 7 (mean 7.13), and the median planned treatment volume was 6.12 cm3 (range 0.42–57.83 cm3) per patient. The median clinical follow-up was 4.1 months (range 0.1–40.70 months). Actuarial tumor control was calculated to be 92.4% at 6 months, 84.8% at 12 months, and 74.9% at 24 months post-GKS. The median OS was found to be 4.73 months (range 0.4–41.8 months). Multivariate analysis demonstrated that RPA class was a significant predictor of death (HR = 2.263, p = 0.038). Number of lesions, tumor histology, Graded Prognostic Assessment score, prior whole-brain radiation therapy, prior resection, prior chemotherapy, patient age, patient sex, controlled primary tumor, extracranial metastases, and planned treatment volume were not significant predictors of OS.

Conclusions

In patients with 5–15 brain metastases at presentation, the number of lesions did not predict survival after GKS; however, the RPA class was predictive of OS in this group of patients. Gamma Knife surgery for such patients offers an excellent rate of local tumor control.

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David J. Salvetti, Tara G. Nagaraja, Carl Levy, Zhiyaun Xu and Jason Sheehan

Object

Increasingly, meningiomas are detected incidentally, prior to symptom development. While these lesions are traditionally managed conservatively until symptoms develop or lesion growth occurs, it is conceivable that patients at high risk for symptom development may benefit from earlier intervention prior to the appearance of symptoms. However, little research has been performed to determine whether Gamma Knife surgery (GKS) can alter the rate of symptom development in such patients.

Methods

A retrospective case study was performed by screening the University of Virginia GKS database for patients treated for asymptomatic meningiomas. From the patient's medical records, pertinent demographic and treatment information was obtained. Yearly follow-up MRI had been performed to assess tumor control and detect signs of radiation-induced injury. Clinical follow-up via neurological examination had been performed to assess symptom development.

Results

Forty-two patients, 33 females (78.6%) and 9 males (21.4%), with 42 asymptomatic meningiomas were included in the analysis. The median age at GKS was 53 years. The most common lesion location was the cerebral convexities (10 lesions [23.8%]), and the median lesion size was 4.0 ml. The median duration of imaging and clinical follow-ups was 59 and 76 months, respectively. During the follow-up period, 1 tumor (2.4%) increased in size, 2 patients (4.8%) demonstrated symptoms, and 1 patient (2.4%) exhibited possible signs of radiation-induced injury. Thus, actuarial tumor control rates were 100%, 95.7%, and 95.7% for 2, 5, and 10 years, respectively. Actuarial symptom control at 5 and 10 years was 97% and 93.1%, respectively. Overall progression-free survival was 91.1% and 77.8% at 5 and 10 years, respectively.

Conclusions

Compared with published rates of symptom development in patients with untreated meningiomas, results in this study indicated that patients with asymptomatic lesions may benefit from prophylactic radiosurgery prior to the appearance of symptoms. Additionally, GKS is a treatment option that offers low morbidity.

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David J. Salvetti, Zachary J. Tempel, Ezequiel Goldschmidt, Nicole A. Colwell, Federico Angriman, David M. Panczykowski, Nitin Agarwal, Adam S. Kanter and David O. Okonkwo

OBJECTIVE

Nutritional deficiency negatively affects outcomes in many health conditions. In spine surgery, evidence linking preoperative nutritional deficiency to postoperative surgical site infection (SSI) has been limited to small retrospective studies. Authors of the current study analyzed a large consecutive cohort of patients who had undergone elective spine surgery to determine the relationship between a serum biomarker of nutritional status (preoperative prealbumin levels) and SSI.

METHODS

The authors conducted a retrospective review of the electronic medical charts of patients who had undergone posterior spinal surgeries and whose preoperative prealbumin level was available. Additional data pertinent to the risk of SSI were also collected. Patients who developed a postoperative SSI were identified, and risk factors for postoperative SSI were analyzed. Nutritional deficiency was defined as a preoperative serum prealbumin level ≤ 20 mg/dl.

RESULTS

Among a consecutive series of 387 patients who met the study criteria for inclusion, the infection rate for those with preoperative prealbumin ≤ 20 mg/dl was 17.8% (13/73), versus 4.8% (15/314) for those with preoperative prealbumin > 20 mg/dl. On univariate and multivariate analysis a low preoperative prealbumin level was a risk factor for postoperative SSI with a crude OR of 4.29 (p < 0.01) and an adjusted OR of 3.28 (p = 0.02). In addition, several previously known risk factors for infection, including diabetes, spinal fusion, and number of operative levels, were significant for the development of an SSI.

CONCLUSIONS

In this consecutive series, preoperative prealbumin levels, a serum biomarker of nutritional status, correlated with the risk of SSI in elective spine surgery. Prehabilitation before spine surgery, including strategies to improve nutritional status in patients with nutritional deficiencies, may increase value and improve spine care.

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Gurpreet S. Gandhoke, Jason S. Hauptman, David J. Salvetti, Gregory M. Weiner, Ashok Panigrahy, Sabri Yilmaz and Ian F. Pollack

The authors report a unique case of a transosseous CSF fistula that was detected more than 10 years after treatment of a symptomatic Chiari I malformation. This lesion initially presented as an intraosseous cystic lesion involving the C-2 vertebra, which was found to communicate freely with the subarachnoid space through a tiny dural opening. Surgical management involved hemilaminectomy and repair of the dural defect followed by reinforcement of the bony defect with demineralized bone matrix. Following closure of the fistula, symptoms of elevated intracranial pressure developed, necessitating a ventriculoperitoneal shunt for CSF diversion.