Cauda equina syndrome (CES) is defined as the constellation of symptoms that includes low-back pain, sciatica, saddle anesthesia, decreased rectal tone and perineal reflexes, bowel and bladder dysfunction, and variable amounts of lower-extremity weakness. There are several causes of this syndrome including trauma, central disc protrusion, hemorrhage, and neoplastic invasion. In this manuscript the authors reviewed CES in the setting of both primary and secondary neoplasms. They examined the various primary tumor types in this region as well as those representative of metastatic spread. Both surgical and nonsurgical management in this setting were studied.
Carlos A. Bagley and Ziya L. Gokaslan
Carlos A. Bagley, Markus J. Bookland, Jonathan A. Pindrik, Tolga Ozmen, Ziya L. Gokaslan and Timothy F. Witham
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 μL 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 μL 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.
Carlos A. Bagley, Markus J. Bookland, Jonathan A. Pindrik, Tolga Ozmen, Ziya L. Gokaslan, Jean-Paul Wolinsky and Timothy F. Witham
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.
Ryan M. Kretzer, Daniel M. Sciubba, Carlos A. Bagley, Jean-Paul Wolinsky, Ziya L. Gokaslan and Ira M. Garonzik
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 pull-out, 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.
Ajay Mantha, Federico G. Legnani, Carlos A. Bagley, Gary L. Gallia, Ira Garonzik, Gustavo Pradilla, Eric Amundson, Betty M. Tyler, Henry Brem and Ziya L. Gokaslan
Object. Although metastatic spinal disease constitutes a significant percentage of all spinal column tumors, an accessible and reproducible animal model has not been reported. In this study the authors describe the technique for creating an intraosseous spinal tumor model in rats and present a functional and histological analysis.
Methods. Eighteen female Fischer 344 rats were randomized into two groups. Group 1 animals underwent a transabdominal exposure and implantation of CRL-1666 breast adenocarcinoma into the L-6 vertebral body (VB). Animals in Group 2 underwent a sham operation. Hindlimb function was tested daily by using the Basso-Beattie-Bresnahan scale. Sixteen days after tumor implantation, animals were killed and their spines were removed for histological assessment. Statistical analysis was performed using the Wilcoxon signed-rank test.
By Day 15 functional analysis showed a significant decrease in motor function in Group 1 animals (median functional score 2 of 21) compared with Group 2 rats (median functional score 21 of 21) (p = 0.0217). The onset of paraparesis in Group 1 occurred within 14 to 16 days of surgery. Histopathological analysis showed tumor proliferation through the VB and into the spinal canal, with marked osteolytic activity and spinal cord compression.
Conclusions. Analysis of these findings demonstrates the consistency of tumor growth in this model and validates the utility of functional testing for onset of paresis. This new rat model allows for the preclinical evaluation of novel therapeutic treatments for patients harboring metastatic spine disease.
Owoicho Adogwa, Ricardo K. Carr, Katherine Kudyba, Isaac Karikari, Carlos A. Bagley, Ziya L. Gokaslan, Nicholas Theodore and Joseph S. Cheng
Same-level recurrent lumbar stenosis, pseudarthrosis, and adjacent-segment disease (ASD) are potential complications that can occur after index lumbar spine surgery, leading to significant discomfort and radicular pain. While numerous studies have demonstrated excellent results following index lumbar spine surgery in elderly patients (age > 65 years), the effectiveness of revision lumbar surgery in this cohort remains unclear. The aim of this study was to assess the long-term effectiveness of revision lumbar decompression and fusion in the treatment of symptomatic pseudarthrosis, ASD, and same-level recurrent stenosis, using validated patient-reported outcomes.
After a review of the institutional database, 69 patients who had undergone revision neural decompression and instrumented fusion for ASD (28 patients), pseudarthrosis (17 patients), or same-level recurrent stenosis (24 patients) were included in this study. Baseline and 2-year scores on the visual analog scale for leg pain (VAS-LP), VAS for back pain (VAS-BP), Oswestry Disability Index (ODI), and Zung Self-Rating Depression Scale (SDS) as well as the time to narcotic independence, time to return to baseline activity level, health state utility (EQ-5D, the EuroQol-5D health survey), and physical and mental component summary scores of the 12-Item Short-Form Health Survey (SF-12 PCS and MCS) were assessed.
Compared with the preoperative status, VAS-BP was significantly improved 2 years after surgery for ASD (mean ± standard deviation 9 ± 2 vs 4.01 ± 2.56, p = 0.001), pseudarthrosis (7.41 ± 1 vs 5.52 ± 3.08, p = 0.02), and same-level recurrent stenosis (7 ± 2.00 vs 5.00 ± 2.34, p = 0.003). The 2-year ODI was also significantly improved after surgery for ASD (29 ± 9 vs 23.10 ± 10.18, p = 0.001), pseudarthrosis (28.47 ± 5.85 vs 24.41 ± 7.75, p = 0.001), and same-level recurrent stenosis (30.83 ± 5.28 vs 26.29 ± 4.10, p = 0.003). The Zung SDS score and SF-12 MCS did not change appreciably after surgery in any of the cohorts, with an overall mean 2-year change of 1.01 ± 5.32 (p = 0.46) and 2.02 ± 9.25 (p = 0.22), respectively.
Data in this study suggest that revision lumbar decompression and extension of fusion for symptomatic pseudarthrosis, ASD, and same-level recurrent stenosis provides improvement in low-back pain, disability, and quality of life and should be considered a viable treatment option for elderly patients with persistent or recurrent back and radicular pain. Mental health symptoms may be more refractory to revision surgery.