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, Jonathan A. Pindrik, Markus J. Bookland, Joaquin Q. Camara-Quintana and Benjamin S. Carson
Achondroplasia is the most common hereditary form of dwarfism, and is characterized by short stature, macrocephaly, and a myriad of skeletal abnormalities. In the pediatric population, stenosis and compression at the level of the cervicomedullary junction commonly occurs. The goal in this study was to assess the outcomes in children with achondroplasia who underwent cervicomedullary decompression.
Forty-three pediatric patients with heterozygous achondroplasia and foramen magnum stenosis underwent 45 cervicomedullary decompressions at the authors’ institution over an 11-year period. After surgical decompression, complete resolution or partial improvement in the preoperative symptoms was observed in all patients. There were no deaths in the treated patients. The surgical morbidity rate was low and usually consisted of a cerebrospinal fluid (CSF) leak in patients in whom the dura mater had been opened (either intentionally or accidentally). This problem was successfully managed in all cases with local measures (wound oversewing) or CSF diversion.
In this review the authors demonstrate that decompression of the cervicomedullary junction in the setting of achondroplasia may be accomplished safely with significant clinical benefit and minimal morbidity.
Owoicho Adogwa, Aladine A. Elsamadicy, Jing L. Han, Joseph Cheng, Isaac Karikari and Carlos A. Bagley
With the recent passage of the Patient Protection and Affordable Care Act, there has been a dramatic shift toward critical analyses of quality and longitudinal assessment of subjective and objective outcomes after lumbar spine surgery. Accordingly, the emergence and routine use of real-world institutional registries have been vital to the longitudinal assessment of quality. However, prospectively obtaining longitudinal outcomes for patients at 24 months after spine surgery remains a challenge. The aim of this study was to assess if 12-month measures of treatment effectiveness accurately predict long-term outcomes (24 months).
A nationwide, multiinstitutional, prospective spine outcomes registry was used for this study. Enrollment criteria included available demographic, surgical, and clinical outcomes data. All patients had prospectively collected outcomes measures and a minimum 2-year follow-up. Patient-reported outcomes instruments (Oswestry Disability Index [ODI], SF-36, and visual analog scale [VAS]-back pain/leg pain) were completed before surgery and then at 3, 6, 12, and 24 months after surgery. The Health Transition Index of the SF-36 was used to determine the 1- and 2-year minimum clinically important difference (MCID), and logistic regression modeling was performed to determine if achieving MCID at 1 year adequately predicted improvement and achievement of MCID at 24 months.
The study group included 969 patients: 300 patients underwent anterior lumbar interbody fusion (ALIF), 606 patients underwent transforaminal lumbar interbody fusion (TLIF), and 63 patients underwent lateral interbody fusion (LLIF). There was a significant correlation between the 12- and 24-month ODI (r = 0.82; p < 0.0001), SF-36 Physical Component Summary score (r = 0.89; p < 0.0001), VAS-back pain (r = 0.90; p < 0.0001), and VAS-leg pain (r = 0.85; p < 0.0001). For the ALIF cohort, patients achieving MCID thresholds for ODI at 12 months were 13-fold (p < 0.0001) more likely to achieve MCID at 24 months. Similarly, for the TLIF and LLIF cohorts, patients achieving MCID thresholds for ODI at 12 months were 13-fold and 14-fold (p < 0.0001) more likely to achieve MCID at 24 months. Outcome measures obtained at 12 months postoperatively are highly predictive of 24-month outcomes, independent of the surgical procedure.
In a multiinstitutional prospective study, patient-centered measures of surgical effectiveness obtained at 12 months adequately predict long-term (24-month) outcomes after lumbar spine surgery. Patients achieving MCID at 1 year were more likely to report meaningful and durable improvement at 24 months, suggesting that the 12-month time point is sufficient to identify effective versus ineffective patient care.
Joel R. Martin, Owoicho Adogwa, Christopher R. Brown, Maragatha Kuchibhatla, Carlos A. Bagley, Shivanand P. Lad and Oren N. Gottfried
Recent studies have reported that the local delivery of vancomycin powder is associated with a decrease in spinal surgical site infection. This retrospective cohort study compares posterior cervical fusion cases before and after the routine application of spinal vancomycin powder to evaluate the ability of local vancomycin powder to prevent deep wound infection after posterior cervical spinal fusion.
Posterior cervical fusion spinal surgeries performed at a single institution were reviewed from January 2011 to July 2013. Each cohort's baseline characteristics, operative data, and rates of wound infection were compared. Associations between infection and vancomycin powder, with and without propensity score adjustment for risk factors, were determined using logistic regression.
A total of 289 patients (174 untreated and 115 treated with vancomycin powder) were included in the study. The cohorts were similar in terms of baseline and operative variables. No significant change in deep wound infection rate was seen between the control group (6.9%) and intervention group (5.2%, p = 0.563). Logistic regression, with and without propensity score adjustment, demonstrated that the use of vancomycin powder did not impact the development of surgical site infection (OR 0.743 [95% CI 0.270–2.04], p = 0.564) and (OR 0.583 [95% CI 0.198–1.718], p = 0.328), respectively.
Within the context of an ongoing debate on the effectiveness of locally administered vancomycin powder, the authors found no significant difference in the incidence of deep wound infection rates after posterior cervical fusion surgery with routine use of locally applied vancomycin powder. Future prospective randomized series are needed to corroborate these results.
Isaac O. Karikari, Ankit I. Mehta, Can Solakoglu, Carlos A. Bagley, Michael C. Ain and Oren N. Gottfried
Spinopelvic parameters in children with achondroplasia have not been described. Because they observed a unique sagittal spinopelvic phenotype in some achondroplastic children with very horizontal sacrums, the authors sought to quantify the spinopelvic parameters in a pediatric patient population.
A retrospective review was performed to identify all children (age range 1 month–10 years) with a diagnosis of achondroplasia between 2004 and 2009. Clinical and radiographic data were analyzed for age, sex, lumbar lordosis (LL), thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), sacral slope (SS), pelvic tilt (PT), and pelvic incidence (PI). Differences among these variables were analyzed using a 2-tailed, unpaired Student t-test.
Forty children, 23 males and 17 females, with achondroplasia were identified during the study period. The mean age was 2.6 years. Two groups of patients were identified based on PT (that is, negative or positive tilt and horizontal or not horizontal sacrum). A negative PT was identified in all children with an extremely horizontal sacrum. Seventeen children had a negative PT (mean −16.6°), and the mean parameters in this group were 65.4° for LL, 31.7° for TLK, 18.5° for TK, 43.3° for SS, and 26.4° for PI. Twenty-three children had a positive PT (mean 17.9°), and the mean parameters in this group were 53.4° for LL, 41.5° for TLK, 9.6° for TK, 30.8° for SS, and 43.8° for PI. A statistically significant difference was observed for LL (p = 0.01), TLK (p = 0.05), SS (p = 0.006), PT (p = 0.006), and PI (0.0002).
Spinopelvic parameters in achondroplasia are potentially dichotomous. The future implications of this observation are not known and will need to be explored in future long-term studies that follow pediatric patients with achondroplasia through adulthood.
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.
Gaurav Mavinkurve, Gustavo Pradilla, Federico G. Legnani, Betty M. Tyler, Carlos A. Bagley, Henry Brem and George Jallo
Survival rates for high-grade intramedullary spinal cord tumors (IMSCTs) are approximately 30%, and optimal therapy has yet to be determined. Development of a satisfactory intramedullary tumor model is necessary for testing new therapeutic paradigms that may prolong survival. The authors report the technique, functional progression, radiological appearance, and histopathological features of a novel intramedullary model in rabbits.
Ten New Zealand white rabbits were randomized to receive an intramedullary injection of either 25 µl of VX2 carcinoma cells (500,000 cells; six rabbits) or 25 ml of medium (Dulbecco modified Eagle medium; four rabbits) into the midthoracic spinal cord. Postoperatively the rabbits were evaluated twice daily for neurological deficits. High-resolution magnetic resonance (MR) images were acquired preoperatively and weekly postoperatively until onset of paraparesis, at which point the animals were killed, and the midthoracic spines were processed for histopathological examination.
The VX2-carcinoma cells grew in 100% of animals injected and resulted in a statistically significant mean onset of paraparesis of 16.8 ± 1.7 days (p = 0.0035, log-rank test), compared with animals in the control group in which neurological deficits were absent by Day 45. Contrast-enhanced T1-weighted MR imaging best demonstrated space-occupying intramedullary lesions and histopathological findings confirmed the intramedullary location of the tumor. Animals in the control group exhibited no functional, radiographic, or pathological signs of tumor.
Progression to paraparesis was consistent in all the VX2-injected animals, with predictable onset of paraparesis occurring approximately 17 days postinjection. Histopathological and radiological characteristics of the VX2 intramedullary tumor are comparable with those of aggressive primary human IMSCTs. Establishment of this novel animal tumor model will facilitate the testing of new therapeutic paradigms for the treatment of IMSCTs.
Mark N. Pernik, Luke J. Dosselman, Salah G. Aoun, Adrienne D. Walker, Kristen Hall, Valery Peinado Reyes, David L. McDonagh and Carlos A. Bagley
The aim of this study was to determine if the use of tranexamic acid (TXA) in long-segment spinal fusion surgery can help reduce perioperative blood loss, transfusion requirements, and morbidity.
In this retrospective single-center study, the authors included 119 consecutive patients who underwent thoracolumbar fusion spanning at least 4 spinal levels from October 2016 to February 2019. Blood loss, transfusion requirements, perioperative morbidity, and adverse thrombotic events were compared between a cohort receiving intravenous TXA and a control group that did not.
There was no significant difference in any measure of intraoperative blood loss (1514.3 vs 1209.1 mL, p = 0.29) or transfusion requirement volume between the TXA and control groups despite a higher number of pelvic fusion procedures in the TXA group (85.9% vs 62.5%, p = 0.003). Postoperative transfusion volume was significantly lower in TXA patients (954 vs 572 mL, p = 0.01). There was no difference in the incidence of thrombotic complications between the groups.
TXA appears to provide a protective effect against blood loss in long-segment spine fusion surgery specifically when pelvic dissection and fixation is performed. TXA also seems to decrease postoperative transfusion requirements without increasing the risk of adverse thrombotic events.
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.