Ziya Gokaslan | Brown University (original) (raw)

Papers by Ziya Gokaslan

World Neurosurgery, 2011

Malignant osseous spinal neoplasms are aggressive tumors associated with poor outcomes despite ag... more Malignant osseous spinal neoplasms are aggressive tumors associated with poor outcomes despite aggressive multidisciplinary measures. It remains unknown whether increased local tumor invasion at time of treatment predicts worse survival. The surveillance, epidemiology, and end results (SEER) registry was reviewed to determine whether extent of local tumor invasion at presentation was independently associated with overall survival. The SEER registry (1973-2003) was queried to identify cases of histologically confirmed primary spinal chordoma, chondrosarcoma, osteosarcoma, or Ewing sarcoma. Extent of local invasion was defined at time of care by histology, radiology, or intraoperative assessment and classified as confined (tumor within periosteum), local invasion (extension to surrounding tissues), or distal metastasis. The association of extent of local tumor invasion with overall survival was assessed by Cox analysis. One thousand eight hundred ninety-two patients were identified (414 chordoma, 579 chondrosarcoma, 430 osteosarcoma, 469 Ewing sarcoma). Overall median survival was histology specific (osteosarcoma, 11 months; Ewing sarcoma, 26 months; chondrosarcoma, 37 months; chordoma, 50 months) and correlated with extent of local tissue invasion or metastasis at presentation. Presence of metastasis was associated with marked decrease in survival (P < 0.001) for all tumor types. For patients with isolated spine tumors, neoplasms confined within the periosteum were associated with improved overall survival independent of age, radiotherapy, or surgical resection for chordoma (hazard ratio [HR], 0.50; P = 0.08), chondrosarcoma (HR, 0.62; P = 0.03), and osteosarcoma (HR, 0.68; P = 0.05), but not Ewing sarcoma (HR, 0.62; P = 0.27). The preoperative radiographic recognition of local tissue invasion may identify patients with a more aggressive tumor and help guide the level of aggressiveness in subsequent treatment strategies.

Journal of Spinal Disorders & Techniques, 2009

A retrospective review. To assess the utility of preoperative halo immobilization in the avoidanc... more A retrospective review. To assess the utility of preoperative halo immobilization in the avoidance of swallowing complications-associated occipitocervical fixation. The craniocervical region is commonly affected by a number of pathologic processes. Fixation of the upper cervical spine to the occiput provides an excellent means of treating these conditions. Occipitocervical fixation, however, is associated with a number of potential complications. One under-reported postoperative complication is the swallowing difficulty that some patients experience. Another is the overall patient dissatisfaction with postoperative head position. One means that the authors have used to avoid these complications is the use of preoperative halo vest fixation. In this article, we report our experience with preoperative halo vest immobilization for occipitocervical fusion in 12 consecutive patients over a 5-month period and its effect on postoperative complications. We also report our experience with the index case of this series in which the patient required operative revision because of severe postoperative dysphagia and stridor after an occipitocervical fusion. All patients achieved satisfactory postoperative head position using the preoperative halo immobilization technique. One patient experienced transient dysphagia, which did not require intervention. No patients experienced any complications related to the placement of the halo vest itself. Preoperative halo immobilization allows patients, who are going to have their head permanently fixed in a particular position, to determine if they are able to tolerate the new head position. This allows the surgeon to adjust the head position before permanently locking the patient in the position, if necessary. We, therefore, advocate the use of preoperative halo immobilization as a means of assuring physiologic craniocervical neutrality and the avoidance of the resultant complications.

Journal of Neurosurgery: Spine, 2006

The use of pedicle screws (PSs) for instrument-assisted fusion in the cervical and thoracic spine... more The use of pedicle screws (PSs) for instrument-assisted fusion in the cervical and thoracic spine has increased in recent years, allowing smaller constructs with improved biomechanical stability and repositioning possibilities. In the smaller pedicles of the upper thoracic spine, the placement of PSs can be challenging and may increase the risk of damage to neural structures. As an alternative to PSs, translaminar screws can provide spinal stability, and they may be used when pedicular anatomy precludes successful placement of PSs. The authors describe the technique of translaminar screw placement in the T-1 and T-2 vertebrae. Seven patients underwent cervicothoracic fusion to treat trauma, neoplasm, or degenerative disease. Nineteen translaminar screws were placed, 13 at T-1 and six at T-2. A single asymptomatic T-2 screw violated the ventral laminar cortex and was removed. The mean clinical and radiographic follow up exceeded 14 months, at which time there were no cases of screw pullout, screw fracture, or progressive kyphotic deformity. Rigid fixation with translaminar screws offers an attractive alternative to PS fixation, allowing the creation of sound spinal constructs and minimizing potential neurological morbidity. Their use requires intact posterior elements, and care should be taken to avoid violation of the ventral laminar wall.

Operative Techniques in Neurosurgery, 2004

Infections involving the epidural space of the spinal canal are rare, yet potentially devastating... more Infections involving the epidural space of the spinal canal are rare, yet potentially devastating entities. The incidence of spontaneous epidural abscesses ranges from 0.2 to 1.3 per 10,000 hospital admissions, most commonly affecting those who are immunosuppressed. The overall incidence of epidural abscesses has been found to be on the rise in recent years, due in part to the overall aging of the population, increasing medical use of potent immunosuppressants, increasing numbers of interventional procedures involving the spinal column, and increasing rates of intravenous drug abuse. The cervical spine is affected in approximately 20% of spinal epidural abscesses, and is the least commonly affected vertebral region. In this article we review the clinical presentation and surgical management of epidural abscesses involving the cervical spine. Oper Tech Neurosurg 7:206-211

Journal of Neurosurgery: Spine, 2007

Spinal column metastatic disease clinically affects thousands of cancer patients every year. Loca... more Spinal column metastatic disease clinically affects thousands of cancer patients every year. Local chemotherapy represents a new option in the treatment of metastatic disease of the spine. Despite the clinical impact of metastatic spine disease, the literature currently lacks an accurate animal model for the effective dosing of local chemotherapeutic agents within the vertebral column. Female Fischer 344 rats, weighing 150 to 200 g each, were used in this study. After induction of anesthesia, a transabdominal approach to the ventral vertebral body of L-6 was performed. A small hole was drilled and 5 microL of ReGel (blank polymer), OncoGel (paclitaxel and ReGel) 1.5%, OncoGel 3.0%, or OncoGel 6.0% were immediately injected to determine drug toxicity. Based on these results, efficacy studies were performed by intratumoral injection of 5 microL of ReGel, OncoGel 3.0%, and OncoGel 6.0% on Day 6 in a CRL- 1666 breast adenocarcinoma metastatic spine tumor model. Hind limb function was tested pre- and postoperatively using the Basso-Beattie-Bresnahan rating scale. Histological analysis of the spinal cord and vertebral column was performed when the animal died or was killed. There were no signs of toxicity observed in association with any of the agents under study. No increased benefit was seen in the blank polymer group compared with the control group (tumor only). OncoGel 3.0% and OncoGel 6.0% were effective in delaying the onset of paralysis in the respective study groups. These findings demonstrate the potential benefit of OncoGel in cases of subtotal resections of metastatic spinal column tumors. OncoGel 6.0% is the most efficacious drug concentration and offers the best therapeutic option in this experimental model. These results provide promise for the development of local chemotherapeutic means to treat spinal metastases.

Neurosurgery, 2005

Although the majority of human epidural spinal metastases originate in the vertebral body, curren... more Although the majority of human epidural spinal metastases originate in the vertebral body, current animal models of spinal epidural tumors are limited to extraosseous tumor placement. We investigated the onset of paraparesis, radiographic changes (magnetic resonance imaging [MRI] and computed tomographic [CT] scans), and histopathological findings after intraosseous injection of VX2 carcinoma cells into the lower thoracic vertebrae of rabbits. New Zealand white rabbits (n = 23) were injected with a 15-mul suspension containing 300,000 VX2 carcinoma cells in the lowest thoracic vertebral body. Lower extremity motor function was assessed daily. For the first 3 animals, MRI scans (T2-weighted and T1-weighted +/- gadolinium) were acquired at postoperative day (POD) 14 and at the onset of paraparesis. Noncontrast CT scans were obtained on POD 7 and at the time of paraparesis. At the onset of paraparesis, the animals ware killed and the spines were dissected. After demineralization, hematoxylin and eosin cross sections were obtained. Before the onset of paraparesis, the CT and MRI scans revealed no gross tumor. At the onset of paraparesis, CT scans demonstrated an osteolytic tumor centered at the junction of the left pedicle and vertebral body, and MRI scans demonstrated epidural tumor arising from the body and compressing the spinal cord. Histopathological examination confirmed carcinoma arising from the body and extending into the canal, with widespread osteolytic activity. By POD 28, 72% of the animals had become paraparetic, and by the termination of the experiment on POD 120, 89% had become paraparetic. We established a novel intraosseous intravertebral tumor model in rabbits and characterized it with respect to onset of paraparesis, imaging features, and histopathological findings.

Journal of Neurosurgery: Spine, 2007

Spinal column metastatic disease affects thousands of cancer patients every year. Radiation thera... more Spinal column metastatic disease affects thousands of cancer patients every year. Radiation therapy frequently represents the primary treatment for this condition. Despite the enormous clinical impact of spinal column metastatic disease, the literature currently lacks an accurate animal model for testing the efficacy of irradiation on spinal column metastases. After anesthesia was induced, female Fischer 344 rats underwent a transabdominal approach to the ventral vertebral body (VB) of L-6. A 2- to 3-mm-diameter bur hole was drilled for the implantation of a section of CRL-1666 breast adenocarcinoma. After the animals had recovered from the surgery, they underwent fractionated, single-port radiotherapy beginning on postoperative Day 7. Each group of animals underwent five daily fractions of radiation treatment. Group I animals received a total dose of 10 Gy in 200-cGy daily fractions, Group II animals received a total dose of 20 Gy in 400-cGy daily fractions, and Group III animals received a total dose of 30 Gy in 600-cGy daily fractions. A control group of rats with implanted VB lesions did not receive radiation. To test the effects of radiation toxicity alone, additional rats without implanted tumors received radiation treatments in the same fractions as the rats with tumors. Hindlimb function in all rats was rated before and after radiation treatment using the Basso-Beattie-Bresnahan locomotor rating scale. Histological analysis of spinal cord and vertebral column sections was performed after each animal's death. Functional assessments demonstrated a statistically significant delay in the onset of paresis between the three treatment groups and the control group (tumor implanted but no radiotherapy). The rats in the three treatment groups, however, did not exhibit any significant differences related to hindlimb function. A dose-dependent relationship was found for the percentage of animals who had become paralyzed at the time of death, with all members of the control group and no members of the 30-Gy group exhibiting paralysis. The results of this study do not indicate any overall survival benefit for any level of radiation dose. These findings demonstrate the efficacy of focal spinal irradiation in delaying the onset of paralysis in a rat metastatic spine tumor model, but without a clear survival benefit. Because of the dose-related toxicity observed in the rats treated with 30 Gy, this effect was most profound for the 20-Gy group. This finding parallels the observed clinical course of spinal column metastatic disease in humans and provides a basis for the future comparison of novel local and systemic treatments to augment the observed effects of focal irradiation.

European Spine Journal, 2007

Interbody fusion has become a mainstay of surgical management for lumbar fractures, tumors, spond... more Interbody fusion has become a mainstay of surgical management for lumbar fractures, tumors, spondylosis, spondylolisthesis and deformities. Over the years, it has undergone a number of metamorphoses, as novel instrumentation and approaches have arisen to reduce complications and enhance outcomes. Interbody fusion procedures are common and successful, complications are rare and most often do not involve the interbody device itself. We present here a patient who underwent an anterior L4 corpectomy with Harms cage placement and who later developed a fracture of the lumbar titanium mesh cage (TMC). This report details the presentation and management of this rare complication, as well as discusses the biomechanics underlying this rare instrumentation failure.

Operative Techniques in Neurosurgery, 2004

Infections involving the epidural space of the spinal canal are rare, yet potentially devastating... more Infections involving the epidural space of the spinal canal are rare, yet potentially devastating entities. The incidence of spontaneous epidural abscesses ranges from 0.2 to 1.3 per 10,000 hospital admissions, most commonly affecting those who are immunosuppressed. The overall incidence of epidural abscesses has been found to be on the rise in recent years, due in part to the overall aging of the population, increasing medical use of potent immunosuppressants, increasing numbers of interventional procedures involving the spinal column, and increasing rates of intravenous drug abuse. The cervical spine is affected in approximately 20% of spinal epidural abscesses and is the least commonly affected vertebral region. In this article we review the clinical presentation and surgical management of epidural abscesses involving the cervical spine.

Neurosurgery, 2006

Ependymomas of the conus medullaris-cauda equina-filum terminale region are typically solitary le... more Ependymomas of the conus medullaris-cauda equina-filum terminale region are typically solitary lesions. In this report, we describe the clinical presentation, radiographic findings, operative details, and pathological features of a patient with a conus medullaris ependymoma and a filum terminale lipoma. A 40-year-old woman presented with increasing low back pain and bowel and bladder dysfunction. Magnetic resonance imaging revealed a partially cystic enhancing lesion at the conus medullaris and a T1-weighted hyperintense mass within the filum terminale. An L2-L3 laminotomy/laminoplasty was performed for gross total resection of the mass. Histopathological examination demonstrated a conus medullaris ependymoma and filum terminale lipoma. The patient experienced complete resolution of her preoperative symptoms. Spinal cord ependymomas are almost exclusively single lesions and their coexistence with other pathological entities is rare. In this report, we describe a patient with a concomitant conus medullaris ependymoma and filum terminale lipoma.

Global Spine Journal, 2015

Spine, 2009

Study Design. Reliability analysis based on expert panel case series review and grading per the E... more Study Design. Reliability analysis based on expert panel case series review and grading per the Enneking and Weinstein-Boriani-Biagini classification systems.

Evidence-Based Spine-Care Journal, 2013

Study Type Retrospective cohort.

Spine, 2009

Systematic review of the literature and consensus recommendations by an international expert focu... more Systematic review of the literature and consensus recommendations by an international expert focus group. To review and classify evidence in the literature regarding: (1) the role of neoadjuvant chemotherapy and (2) impact of extent of surgical resection on clinical outcome, particularly survival and local control, in patients with spinal Ewing sarcoma (ES) and osteosarcoma (OS). ES and OS of the spine are currently managed with multimodality treatment involving chemotherapy, radiation therapy, and surgical resection. It is currently unclear if extent of resection, for example, intralesional resection versus marginal or wide resection has an impact on survival or local control of disease. A systematic literature search for the years 1960 to 2008 was performed looking at publications involving treatment of spinal ES and OS. From these 208 articles, 16 were selected for analysis and were reviewed in depth. Studies were presented to a group of spinal oncology experts. Literature was graded for quality, summarized and presented to an international expert group with consensus recommendations generated. For ES of the spine, 10 studies were analyzed. For OS of the spine, 6 studies were analyzed. For both ES and OS of the spine, moderate level evidence supported a strong recommendation that neoadjuvant chemotherapy offers significant improvements in local control and long-term survival and is essential in multimodality management. For spinal ES, very low level evidence supported a weak recommendation that en bloc surgical resection provides improved local control, but not improved overall survival. Radiation therapy for spinal ES may also be used for local control either alone or to supplement incomplete resection. For spinal OS, very low evidence supported a strong recommendation that en bloc resection provides improved local control and potentially improved overall survival. Patients with ES and OS are currently managed with multiple modalities involving surgery, radiation, and chemotherapy. For both histopathologies, advances in chemotherapy have led to the greatest improvements in survival over the last few decades. Neoadjuvant therapy portents the most favorable local control and long-term survival. En bloc surgical resection may improve overall survival and decrease risk of recurrence.

Neurosurgery, 2007

BACKGROUND: Contemporary treatment of intramedullary spinal cord tumors (IMSCTs) involves radical... more BACKGROUND: Contemporary treatment of intramedullary spinal cord tumors (IMSCTs) involves radical or subtotal tumor resection with adjuvant radiation and/or chemotherapy, depending on the tumor's histological type and grade as well as the extent of resection. Despite advances in surgical therapy, this approach continues to have significant morbidity. Although previous research is limited, identifying reliable predictors of functional status after tumor resection would be clinically useful for perioperative modification strategies. METHODS: All patients who underwent surgery for IMSCTs at an academic tertiary care institution between 1995 and 2004 were retrospectively reviewed, and predictors of postoperative neurological functional status were assessed by multivariate logistical regression analysis. Neurological status was gauged by the ability to walk without assistance at the time of the last follow-up visit. RESULTS: Seventy-eight IMSCT resections were performed during the study period. Preoperative (on the d of or the d before surgery) serum glucose greater than 170 mg/dl (relative risk, 0.03; 95% confidence interval, 0.00-0.27; P ϭ 0.001) and preoperative radiation therapy (relative risk, 0.02; 95% confidence interval, 0.00-0.39, P ϭ 0.012) were independently associated with poor functional status postoperatively. The ability to walk unassisted before surgery (relative risk, 17.1; 95% confidence interval, 1.89-154.5, P ϭ 0.012), on other hand, was the only positive predictor of the ability to walk unassisted at the time of the last follow-up visit. CONCLUSION: This study suggests that early surgical intervention after the onset of symptoms for patients with IMSCT may help preserve ambulatory function. Deferral of preoperative radiation therapy for less radiosensitive tumors and strict perioperative glucose control may also help maximize a patient's subsequent ambulatory status.

Neurological Research, 2009

Cervical spondylosis is a common degenerative condition that is a significant cause of morbidity.... more Cervical spondylosis is a common degenerative condition that is a significant cause of morbidity. This review discusses the pathophysiology and natural history of cervical spondylotic myelopathy and focuses on the current literature evaluating the clinical management of these patients.

World Neurosurgery, 2011

Malignant osseous spinal neoplasms are aggressive tumors associated with poor outcomes despite ag... more Malignant osseous spinal neoplasms are aggressive tumors associated with poor outcomes despite aggressive multidisciplinary measures. It remains unknown whether increased local tumor invasion at time of treatment predicts worse survival. The surveillance, epidemiology, and end results (SEER) registry was reviewed to determine whether extent of local tumor invasion at presentation was independently associated with overall survival. The SEER registry (1973-2003) was queried to identify cases of histologically confirmed primary spinal chordoma, chondrosarcoma, osteosarcoma, or Ewing sarcoma. Extent of local invasion was defined at time of care by histology, radiology, or intraoperative assessment and classified as confined (tumor within periosteum), local invasion (extension to surrounding tissues), or distal metastasis. The association of extent of local tumor invasion with overall survival was assessed by Cox analysis. One thousand eight hundred ninety-two patients were identified (414 chordoma, 579 chondrosarcoma, 430 osteosarcoma, 469 Ewing sarcoma). Overall median survival was histology specific (osteosarcoma, 11 months; Ewing sarcoma, 26 months; chondrosarcoma, 37 months; chordoma, 50 months) and correlated with extent of local tissue invasion or metastasis at presentation. Presence of metastasis was associated with marked decrease in survival (P < 0.001) for all tumor types. For patients with isolated spine tumors, neoplasms confined within the periosteum were associated with improved overall survival independent of age, radiotherapy, or surgical resection for chordoma (hazard ratio [HR], 0.50; P = 0.08), chondrosarcoma (HR, 0.62; P = 0.03), and osteosarcoma (HR, 0.68; P = 0.05), but not Ewing sarcoma (HR, 0.62; P = 0.27). The preoperative radiographic recognition of local tissue invasion may identify patients with a more aggressive tumor and help guide the level of aggressiveness in subsequent treatment strategies.

Journal of Spinal Disorders & Techniques, 2009

A retrospective review. To assess the utility of preoperative halo immobilization in the avoidanc... more A retrospective review. To assess the utility of preoperative halo immobilization in the avoidance of swallowing complications-associated occipitocervical fixation. The craniocervical region is commonly affected by a number of pathologic processes. Fixation of the upper cervical spine to the occiput provides an excellent means of treating these conditions. Occipitocervical fixation, however, is associated with a number of potential complications. One under-reported postoperative complication is the swallowing difficulty that some patients experience. Another is the overall patient dissatisfaction with postoperative head position. One means that the authors have used to avoid these complications is the use of preoperative halo vest fixation. In this article, we report our experience with preoperative halo vest immobilization for occipitocervical fusion in 12 consecutive patients over a 5-month period and its effect on postoperative complications. We also report our experience with the index case of this series in which the patient required operative revision because of severe postoperative dysphagia and stridor after an occipitocervical fusion. All patients achieved satisfactory postoperative head position using the preoperative halo immobilization technique. One patient experienced transient dysphagia, which did not require intervention. No patients experienced any complications related to the placement of the halo vest itself. Preoperative halo immobilization allows patients, who are going to have their head permanently fixed in a particular position, to determine if they are able to tolerate the new head position. This allows the surgeon to adjust the head position before permanently locking the patient in the position, if necessary. We, therefore, advocate the use of preoperative halo immobilization as a means of assuring physiologic craniocervical neutrality and the avoidance of the resultant complications.

Journal of Neurosurgery: Spine, 2006

The use of pedicle screws (PSs) for instrument-assisted fusion in the cervical and thoracic spine... more The use of pedicle screws (PSs) for instrument-assisted fusion in the cervical and thoracic spine has increased in recent years, allowing smaller constructs with improved biomechanical stability and repositioning possibilities. In the smaller pedicles of the upper thoracic spine, the placement of PSs can be challenging and may increase the risk of damage to neural structures. As an alternative to PSs, translaminar screws can provide spinal stability, and they may be used when pedicular anatomy precludes successful placement of PSs. The authors describe the technique of translaminar screw placement in the T-1 and T-2 vertebrae. Seven patients underwent cervicothoracic fusion to treat trauma, neoplasm, or degenerative disease. Nineteen translaminar screws were placed, 13 at T-1 and six at T-2. A single asymptomatic T-2 screw violated the ventral laminar cortex and was removed. The mean clinical and radiographic follow up exceeded 14 months, at which time there were no cases of screw pullout, screw fracture, or progressive kyphotic deformity. Rigid fixation with translaminar screws offers an attractive alternative to PS fixation, allowing the creation of sound spinal constructs and minimizing potential neurological morbidity. Their use requires intact posterior elements, and care should be taken to avoid violation of the ventral laminar wall.

Operative Techniques in Neurosurgery, 2004

Infections involving the epidural space of the spinal canal are rare, yet potentially devastating... more Infections involving the epidural space of the spinal canal are rare, yet potentially devastating entities. The incidence of spontaneous epidural abscesses ranges from 0.2 to 1.3 per 10,000 hospital admissions, most commonly affecting those who are immunosuppressed. The overall incidence of epidural abscesses has been found to be on the rise in recent years, due in part to the overall aging of the population, increasing medical use of potent immunosuppressants, increasing numbers of interventional procedures involving the spinal column, and increasing rates of intravenous drug abuse. The cervical spine is affected in approximately 20% of spinal epidural abscesses, and is the least commonly affected vertebral region. In this article we review the clinical presentation and surgical management of epidural abscesses involving the cervical spine. Oper Tech Neurosurg 7:206-211

Journal of Neurosurgery: Spine, 2007

Spinal column metastatic disease clinically affects thousands of cancer patients every year. Loca... more Spinal column metastatic disease clinically affects thousands of cancer patients every year. Local chemotherapy represents a new option in the treatment of metastatic disease of the spine. Despite the clinical impact of metastatic spine disease, the literature currently lacks an accurate animal model for the effective dosing of local chemotherapeutic agents within the vertebral column. Female Fischer 344 rats, weighing 150 to 200 g each, were used in this study. After induction of anesthesia, a transabdominal approach to the ventral vertebral body of L-6 was performed. A small hole was drilled and 5 microL of ReGel (blank polymer), OncoGel (paclitaxel and ReGel) 1.5%, OncoGel 3.0%, or OncoGel 6.0% were immediately injected to determine drug toxicity. Based on these results, efficacy studies were performed by intratumoral injection of 5 microL of ReGel, OncoGel 3.0%, and OncoGel 6.0% on Day 6 in a CRL- 1666 breast adenocarcinoma metastatic spine tumor model. Hind limb function was tested pre- and postoperatively using the Basso-Beattie-Bresnahan rating scale. Histological analysis of the spinal cord and vertebral column was performed when the animal died or was killed. There were no signs of toxicity observed in association with any of the agents under study. No increased benefit was seen in the blank polymer group compared with the control group (tumor only). OncoGel 3.0% and OncoGel 6.0% were effective in delaying the onset of paralysis in the respective study groups. These findings demonstrate the potential benefit of OncoGel in cases of subtotal resections of metastatic spinal column tumors. OncoGel 6.0% is the most efficacious drug concentration and offers the best therapeutic option in this experimental model. These results provide promise for the development of local chemotherapeutic means to treat spinal metastases.

Neurosurgery, 2005

Although the majority of human epidural spinal metastases originate in the vertebral body, curren... more Although the majority of human epidural spinal metastases originate in the vertebral body, current animal models of spinal epidural tumors are limited to extraosseous tumor placement. We investigated the onset of paraparesis, radiographic changes (magnetic resonance imaging [MRI] and computed tomographic [CT] scans), and histopathological findings after intraosseous injection of VX2 carcinoma cells into the lower thoracic vertebrae of rabbits. New Zealand white rabbits (n = 23) were injected with a 15-mul suspension containing 300,000 VX2 carcinoma cells in the lowest thoracic vertebral body. Lower extremity motor function was assessed daily. For the first 3 animals, MRI scans (T2-weighted and T1-weighted +/- gadolinium) were acquired at postoperative day (POD) 14 and at the onset of paraparesis. Noncontrast CT scans were obtained on POD 7 and at the time of paraparesis. At the onset of paraparesis, the animals ware killed and the spines were dissected. After demineralization, hematoxylin and eosin cross sections were obtained. Before the onset of paraparesis, the CT and MRI scans revealed no gross tumor. At the onset of paraparesis, CT scans demonstrated an osteolytic tumor centered at the junction of the left pedicle and vertebral body, and MRI scans demonstrated epidural tumor arising from the body and compressing the spinal cord. Histopathological examination confirmed carcinoma arising from the body and extending into the canal, with widespread osteolytic activity. By POD 28, 72% of the animals had become paraparetic, and by the termination of the experiment on POD 120, 89% had become paraparetic. We established a novel intraosseous intravertebral tumor model in rabbits and characterized it with respect to onset of paraparesis, imaging features, and histopathological findings.

Journal of Neurosurgery: Spine, 2007

Spinal column metastatic disease affects thousands of cancer patients every year. Radiation thera... more Spinal column metastatic disease affects thousands of cancer patients every year. Radiation therapy frequently represents the primary treatment for this condition. Despite the enormous clinical impact of spinal column metastatic disease, the literature currently lacks an accurate animal model for testing the efficacy of irradiation on spinal column metastases. After anesthesia was induced, female Fischer 344 rats underwent a transabdominal approach to the ventral vertebral body (VB) of L-6. A 2- to 3-mm-diameter bur hole was drilled for the implantation of a section of CRL-1666 breast adenocarcinoma. After the animals had recovered from the surgery, they underwent fractionated, single-port radiotherapy beginning on postoperative Day 7. Each group of animals underwent five daily fractions of radiation treatment. Group I animals received a total dose of 10 Gy in 200-cGy daily fractions, Group II animals received a total dose of 20 Gy in 400-cGy daily fractions, and Group III animals received a total dose of 30 Gy in 600-cGy daily fractions. A control group of rats with implanted VB lesions did not receive radiation. To test the effects of radiation toxicity alone, additional rats without implanted tumors received radiation treatments in the same fractions as the rats with tumors. Hindlimb function in all rats was rated before and after radiation treatment using the Basso-Beattie-Bresnahan locomotor rating scale. Histological analysis of spinal cord and vertebral column sections was performed after each animal's death. Functional assessments demonstrated a statistically significant delay in the onset of paresis between the three treatment groups and the control group (tumor implanted but no radiotherapy). The rats in the three treatment groups, however, did not exhibit any significant differences related to hindlimb function. A dose-dependent relationship was found for the percentage of animals who had become paralyzed at the time of death, with all members of the control group and no members of the 30-Gy group exhibiting paralysis. The results of this study do not indicate any overall survival benefit for any level of radiation dose. These findings demonstrate the efficacy of focal spinal irradiation in delaying the onset of paralysis in a rat metastatic spine tumor model, but without a clear survival benefit. Because of the dose-related toxicity observed in the rats treated with 30 Gy, this effect was most profound for the 20-Gy group. This finding parallels the observed clinical course of spinal column metastatic disease in humans and provides a basis for the future comparison of novel local and systemic treatments to augment the observed effects of focal irradiation.

European Spine Journal, 2007

Interbody fusion has become a mainstay of surgical management for lumbar fractures, tumors, spond... more Interbody fusion has become a mainstay of surgical management for lumbar fractures, tumors, spondylosis, spondylolisthesis and deformities. Over the years, it has undergone a number of metamorphoses, as novel instrumentation and approaches have arisen to reduce complications and enhance outcomes. Interbody fusion procedures are common and successful, complications are rare and most often do not involve the interbody device itself. We present here a patient who underwent an anterior L4 corpectomy with Harms cage placement and who later developed a fracture of the lumbar titanium mesh cage (TMC). This report details the presentation and management of this rare complication, as well as discusses the biomechanics underlying this rare instrumentation failure.

Operative Techniques in Neurosurgery, 2004

Infections involving the epidural space of the spinal canal are rare, yet potentially devastating... more Infections involving the epidural space of the spinal canal are rare, yet potentially devastating entities. The incidence of spontaneous epidural abscesses ranges from 0.2 to 1.3 per 10,000 hospital admissions, most commonly affecting those who are immunosuppressed. The overall incidence of epidural abscesses has been found to be on the rise in recent years, due in part to the overall aging of the population, increasing medical use of potent immunosuppressants, increasing numbers of interventional procedures involving the spinal column, and increasing rates of intravenous drug abuse. The cervical spine is affected in approximately 20% of spinal epidural abscesses and is the least commonly affected vertebral region. In this article we review the clinical presentation and surgical management of epidural abscesses involving the cervical spine.

Neurosurgery, 2006

Ependymomas of the conus medullaris-cauda equina-filum terminale region are typically solitary le... more Ependymomas of the conus medullaris-cauda equina-filum terminale region are typically solitary lesions. In this report, we describe the clinical presentation, radiographic findings, operative details, and pathological features of a patient with a conus medullaris ependymoma and a filum terminale lipoma. A 40-year-old woman presented with increasing low back pain and bowel and bladder dysfunction. Magnetic resonance imaging revealed a partially cystic enhancing lesion at the conus medullaris and a T1-weighted hyperintense mass within the filum terminale. An L2-L3 laminotomy/laminoplasty was performed for gross total resection of the mass. Histopathological examination demonstrated a conus medullaris ependymoma and filum terminale lipoma. The patient experienced complete resolution of her preoperative symptoms. Spinal cord ependymomas are almost exclusively single lesions and their coexistence with other pathological entities is rare. In this report, we describe a patient with a concomitant conus medullaris ependymoma and filum terminale lipoma.

Global Spine Journal, 2015

Spine, 2009

Study Design. Reliability analysis based on expert panel case series review and grading per the E... more Study Design. Reliability analysis based on expert panel case series review and grading per the Enneking and Weinstein-Boriani-Biagini classification systems.

Evidence-Based Spine-Care Journal, 2013

Study Type Retrospective cohort.

Spine, 2009

Systematic review of the literature and consensus recommendations by an international expert focu... more Systematic review of the literature and consensus recommendations by an international expert focus group. To review and classify evidence in the literature regarding: (1) the role of neoadjuvant chemotherapy and (2) impact of extent of surgical resection on clinical outcome, particularly survival and local control, in patients with spinal Ewing sarcoma (ES) and osteosarcoma (OS). ES and OS of the spine are currently managed with multimodality treatment involving chemotherapy, radiation therapy, and surgical resection. It is currently unclear if extent of resection, for example, intralesional resection versus marginal or wide resection has an impact on survival or local control of disease. A systematic literature search for the years 1960 to 2008 was performed looking at publications involving treatment of spinal ES and OS. From these 208 articles, 16 were selected for analysis and were reviewed in depth. Studies were presented to a group of spinal oncology experts. Literature was graded for quality, summarized and presented to an international expert group with consensus recommendations generated. For ES of the spine, 10 studies were analyzed. For OS of the spine, 6 studies were analyzed. For both ES and OS of the spine, moderate level evidence supported a strong recommendation that neoadjuvant chemotherapy offers significant improvements in local control and long-term survival and is essential in multimodality management. For spinal ES, very low level evidence supported a weak recommendation that en bloc surgical resection provides improved local control, but not improved overall survival. Radiation therapy for spinal ES may also be used for local control either alone or to supplement incomplete resection. For spinal OS, very low evidence supported a strong recommendation that en bloc resection provides improved local control and potentially improved overall survival. Patients with ES and OS are currently managed with multiple modalities involving surgery, radiation, and chemotherapy. For both histopathologies, advances in chemotherapy have led to the greatest improvements in survival over the last few decades. Neoadjuvant therapy portents the most favorable local control and long-term survival. En bloc surgical resection may improve overall survival and decrease risk of recurrence.

Neurosurgery, 2007

BACKGROUND: Contemporary treatment of intramedullary spinal cord tumors (IMSCTs) involves radical... more BACKGROUND: Contemporary treatment of intramedullary spinal cord tumors (IMSCTs) involves radical or subtotal tumor resection with adjuvant radiation and/or chemotherapy, depending on the tumor's histological type and grade as well as the extent of resection. Despite advances in surgical therapy, this approach continues to have significant morbidity. Although previous research is limited, identifying reliable predictors of functional status after tumor resection would be clinically useful for perioperative modification strategies. METHODS: All patients who underwent surgery for IMSCTs at an academic tertiary care institution between 1995 and 2004 were retrospectively reviewed, and predictors of postoperative neurological functional status were assessed by multivariate logistical regression analysis. Neurological status was gauged by the ability to walk without assistance at the time of the last follow-up visit. RESULTS: Seventy-eight IMSCT resections were performed during the study period. Preoperative (on the d of or the d before surgery) serum glucose greater than 170 mg/dl (relative risk, 0.03; 95% confidence interval, 0.00-0.27; P ϭ 0.001) and preoperative radiation therapy (relative risk, 0.02; 95% confidence interval, 0.00-0.39, P ϭ 0.012) were independently associated with poor functional status postoperatively. The ability to walk unassisted before surgery (relative risk, 17.1; 95% confidence interval, 1.89-154.5, P ϭ 0.012), on other hand, was the only positive predictor of the ability to walk unassisted at the time of the last follow-up visit. CONCLUSION: This study suggests that early surgical intervention after the onset of symptoms for patients with IMSCT may help preserve ambulatory function. Deferral of preoperative radiation therapy for less radiosensitive tumors and strict perioperative glucose control may also help maximize a patient's subsequent ambulatory status.

Neurological Research, 2009

Cervical spondylosis is a common degenerative condition that is a significant cause of morbidity.... more Cervical spondylosis is a common degenerative condition that is a significant cause of morbidity. This review discusses the pathophysiology and natural history of cervical spondylotic myelopathy and focuses on the current literature evaluating the clinical management of these patients.