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.
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.
Owoicho Adogwa, Aladine A. Elsamadicy, Victoria D. Vuong, Jared Fialkoff, Joseph Cheng, Isaac O. Karikari and Carlos A. Bagley
Postoperative delirium is common in elderly patients undergoing spine surgery and is associated with a longer and more costly hospital course, functional decline, postoperative institutionalization, and higher likelihood of death within 6 months of discharge. Preoperative cognitive impairment may be a risk factor for the development of postoperative delirium. The aim of this study was to investigate the relationship between baseline cognitive impairment and postoperative delirium in geriatric patients undergoing surgery for degenerative scoliosis.
Elderly patients 65 years and older undergoing a planned elective spinal surgery for correction of adult degenerative scoliosis were enrolled in this study. Preoperative cognition was assessed using the validated Saint Louis University Mental Status (SLUMS) examination. SLUMS comprises 11 questions, with a maximum score of 30 points. Mild cognitive impairment was defined as a SLUMS score between 21 and 26 points, while severe cognitive impairment was defined as a SLUMS score of ≤ 20 points. Normal cognition was defined as a SLUMS score of ≥ 27 points. Delirium was assessed daily using the Confusion Assessment Method (CAM) and rated as absent or present on the basis of CAM. The incidence of delirium was compared in patients with and without baseline cognitive impairment.
Twenty-two patients (18%) developed delirium postoperatively. Baseline demographics, including age, sex, comorbidities, and perioperative variables, were similar in patients with and without delirium. The length of in-hospital stay (mean 5.33 days vs 5.48 days) and 30-day hospital readmission rates (12.28% vs 12%) were similar between patients with and without delirium, respectively. Patients with preoperative cognitive impairment (i.e., a lower SLUMS score) had a higher incidence of postoperative delirium. One- and 2-year patient reported outcomes scores were similar in patients with and without delirium.
Cognitive impairment is a risk factor for the development of postoperative delirium. Postoperative delirium may be associated with decreased preoperative cognitive reserve. Cognitive impairment assessments should be considered in the preoperative evaluations of elderly patients prior to surgery.
Geriatric comanagement reduces perioperative complications and shortens duration of hospital stay after lumbar spine surgery: a prospective single-institution experience
Presented at the 2017 AANS/CNS Joint Section on Disorders of the Spine and Peripheral Nerves
Owoicho Adogwa, Aladine A. Elsamadicy, Victoria D. Vuong, Jessica Moreno, Joseph Cheng, Isaac O. Karikari and Carlos A. Bagley
Geriatric patients undergoing lumbar spine surgery have unique needs due to the physiological changes of aging. They are at risk for adverse outcomes such as delirium, infection, and iatrogenic complications, and these complications, in turn, contribute to the risk of functional decline, nursing home admission, and death. Whether preoperative and perioperative comanagement by a geriatrician reduces the incidence of in-hospital complications and length of in-hospital stay after elective lumbar spine surgery remains unknown.
A unique model of comanagement for elderly patients undergoing lumbar fusion surgery was implemented at a major academic medical center. The Perioperative Optimization of Senior Health (POSH) program was launched with the aim of improving outcomes in elderly patients (> 65 years old) undergoing complex lumbar spine surgery. In this model, a geriatrician evaluates elderly patients preoperatively, in addition to performing routine preoperative anesthesia surgical screening, and comanages them daily throughout the course of their hospital stay to manage medical comorbid conditions and coordinate multidisciplinary rehabilitation along with the neurosurgical team. The first 100 cases were retrospectively reviewed after initiation of the POSH protocol and compared with the immediately preceding 25 cases to assess the incidence of perioperative complications and clinical outcomes.
One hundred twenty-five patients undergoing lumbar decompression and fusion were enrolled in this pilot program. Baseline characteristics were similar between both cohorts. The mean length of in-hospital stay was 30% shorter in the POSH cohort (6.13 vs 8.72 days; p = 0.06). The mean duration of time between surgery and patient mobilization was significantly shorter in the POSH cohort compared with the non-POSH cohort (1.57 days vs 2.77 days; p = 0.02), and the number of steps ambulated on day of discharge was 2-fold higher in the POSH cohort (p = 0.04). Compared with the non-POSH cohort, the majority of patients in the POSH cohort were discharged to home (24% vs 54%; p = 0.01).
Geriatric comanagement reduces the incidence of postoperative complications, shortens the duration of in-hospital stay, and contributes to improved perioperative functional status in elderly patients undergoing elective spinal surgery for the correction of adult degenerative scoliosis.
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.
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.
Disparities in care
John H. Sampson, Carlos A. Bagley and Benjamin S. Carson Sr.
Carlos A. Bagley, Karl F. Kothbauer, Sean Wilson, Markus J. Bookland, Fred J. Epstein and George I. Jallo
Currently, the optimal treatment of children harboring myxopapillary ependymomas of the spinal cord remains somewhat debatable. The authors present a retrospective study in which they evaluated the records of patients in whom resection of these lesions had been performed.
Fourteen pediatric patients who had undergone resection of a spinal cord tumor between September 1982 and July 2004 were identified from the database as having histologically classified myxopapillary ependymomas. There were 10 boys and four girls ranging in age from 7 to 18 years (mean age 12.6 years); 71% of the patients were boys. The clinical presentation of the tumor's course was slow and indolent, and the patients had a mean symptom duration of 19.6 months. Twelve patients, who underwent a total of 16 operations, were available for long-term follow-up review. Thirteen gross-total resections and three subtotal resections were performed. There were no deaths due to surgery. Postoperatively, patients initially remained at their preoperative level of function or improved. Patients who had undergone previous surgery and radiotherapy were treated more conservatively than patients who were undergoing surgery for the first time. Four children experienced significant complications following treatment.
As the authors demonstrate in this study, excellent outcomes may be obtained with the use of aggressive surgical techniques with the goal being that of gross-total resection. Despite the best of resections, however, the risk of recurrence remains. Therefore, periodic neuroimaging surveillance of the neuraxis and close clinical follow up are warranted throughout the patient's life. The role for adjunctive chemo- and radiotherapy remains to be defined in the management of myxopapillary ependymomas.