Claire F. Jones, Jae H. T. Lee, Brian K. Kwon, and Peter A. Cripton
Spinal cord injury (SCI) often results in considerable permanent neurological impairment, and unfortunately, the successful translation of effective treatments from laboratory models to human patients is lacking. This may be partially attributed to differences in anatomy, physiology, and scale between humans and rodent models. One potentially important difference between the rodent and human spinal cord is the presence of a significant CSF volume within the intrathecal space around the human cord. While the CSF may “cushion” the spinal cord, pressure waves within the CSF at the time of injury may contribute to the extent and severity of the primary injury. The objective of this study was to develop a model of contusion SCI in a miniature pig and establish the feasibility of measuring spinal CSF pressure during injury.
A custom weight-drop device was used to apply thoracic contusion SCI to 17 Yucatan miniature pigs. Impact load and velocity were measured. Using fiber optic pressure transducers implanted in the thecal sac, CSF pressures resulting from 2 injury severities (caused by 50-g and 100-g weights released from a 50-cm height) were measured.
The median peak impact loads were 54 N and 132 N for the 50-g and 100-g injuries, respectively. At a nominal 100 mm from the injury epicenter, the authors observed a small negative pressure peak (median −4.6 mm Hg [cranial] and −5.8 mm Hg [caudal] for 50 g; −27.6 mm Hg [cranial] and −27.2 mm Hg [caudal] for 100 g) followed by a larger positive pressure peak (median 110.5 mm Hg [cranial] and 77.1 mm Hg [caudal] for 50 g; 88.4 mm Hg [cranial] and 67.2 mm Hg [caudal] for 100 g) relative to the preinjury pressure. There were no significant differences in peak pressure between the 2 injury severities or the caudal and cranial transducer locations.
A new model of contusion SCI was developed to measure spinal CSF pressures during the SCI event. The results suggest that the Yucatan miniature pig is an appropriate model for studying CSF, spinal cord, and dura interactions during injury. With further development and characterization it may be an appropriate in vivo largeanimal model of SCI to answer questions regarding pathological changes, therapeutic safety, or treatment efficacy, particularly where humanlike dimensions and physiology are important.
Marcus D. Mazur, Walavan Sivakumar, Jay Riva-Cambrin, Jaes Jones, and Douglas L. Brockmeyer
Surgical arthrodesis for pediatric occipitocervical (OC) instability has a high rate of success in a wide variety of challenging circumstances; however, identifying potential risk factors can help to target variables that should be the focus of improvement. The aim of this paper was to examine risk factors predictive of failure in a population of patients who underwent instrumented OC arthrodesis using a uniform surgical philosophy.
The authors conducted a retrospective cohort study of pediatric patients who underwent OC fusion from 2001 to 2013 at a single institution to determine risk factors for surgical failure, defined as reoperation for revision of the arthrodesis or instrumentation. The primary study outcome was either radiographic confirmation of successful OC fusion or surgical failure requiring revision of the arthrodesis or instrumentation. The secondary outcome was the underlying cause of failure (hardware failure, graft failure, or infection). Univariate analysis was performed to assess the association between outcome and patient demographics, cause of OC instability, type of OC instrumentation, bone graft material, biological adjuncts, and complications.
Of the 127 procedures included, 20 (15.7%) involved some form of surgical failure and required revision surgery. Univariate analysis revealed that patients with deep wound infections requiring debridement were more likely to require surgical revision of the hardware or graft (p = 0.002). Subgroup analysis revealed that patients with skeletal dysplasia or congenital spinal anomalies were more likely to develop hardware failure than patients with other causes of OC instability (p = 0.020). Surgical failure was not associated with the method of C-2 fixation, type of rigid OC instrumentation, bone graft material, use of bone morphogenetic protein or biological adjuncts, cause of instability, sex, age, or having previous OC fusion operations.
Pediatric patients in the present cohort with postoperative wound infections requiring surgical debridement had higher surgical failure rates after OC fusion. Those with skeletal dysplasia and congenital spinal anomalies were more likely to require reoperation for hardware failure. Better understanding of the mode of surgical failure may enable surgeons to develop strategies to decrease the need for reoperation in pediatric patients with OC instability.
Jaes C. Jones, Jacob A. Miller, Dattanand M. Sudarshana, Nicolas R. Thompson, Edward C. Benzel, and Thomas E. Mroz
In 2009, 2 randomized controlled trials demonstrated no improvement in pain following vertebral augmentation compared with sham surgery. However, a recent randomized trial demonstrated significant pain relief in patients following vertebroplasty compared to controls treated with conservative medical management. This study is a retrospective review of prospectively collected patient-reported quality of life (QOL) outcomes. The authors hypothesized that vertebral augmentation procedures offer a QOL benefit, but that this benefit would be diminished in patients with a history of depression and/or in patients undergoing vertebral augmentation at more than 1 level.
Multivariable linear regression was used to identify predictors of postoperative pain assessed using the Pain Disability Questionnaire (PDQ), Patient Health Questionnaire 9 (PHQ-9), and EQ-5D scores. Eleven candidate predictors were selected a priori: age, sex, smoking history, coronary artery disease, depression, diabetes, procedure location (thoracic, lumbar), BMI, prior spine surgery, procedure indication (metastases, osteoporosis/osteopenia, other), and number of levels (1, 2, 3, or more).
A total of 143 patients were included in the study. For each 10-year increase in age, postoperative PDQ scores decreased (improved) by 9.7 points (p < 0.001). Patients with osteoporosis/osteopenia had significantly higher (worse) postoperative PDQ scores (+17.97, p = 0.028) than patients with metastatic lesions. Male sex was associated with higher (worse) postoperative PHQ-9 scores (+2.48, p = 0.010). Compared to single-level augmentation, operations at 2 levels were associated with significantly higher PHQ-9 scores (+2.58, p = 0.017). Current smokers had significantly lower PHQ-9 scores (−1.98, p = 0.023) than never smokers. No predictors were associated with significantly different EQ-5D score.
Variables associated with worse postoperative PDQ scores included younger age and osteoporosis/osteopenia. Variables associated with decreased (better) postoperative PHQ-9 scores included female sex, single operative vertebral level, and positive smoking status (i.e., current smoker). These clinically relevant predictors may permit identification of patients who may benefit from vertebral augmentation.
Bryan S. Lee, Jaes Jones, Min Lang, Rebecca Achey, Lu Dai, Darlene A. Lobel, Sean J. Nagel, Andre G. Machado, and Francois Bethoux
Multiple sclerosis (MS) is a chronic autoimmune disease that causes demyelination and axonal loss. Walking difficulties are a common and debilitating symptom of MS; they are usually caused by spastic paresis of the lower extremities. Although intrathecal baclofen (ITB) therapy has been reported to be an effective treatment for spasticity in MS, there is limited published evidence regarding its effects on ambulation. The goal of this study was to characterize ITB therapy outcomes in ambulatory patients with MS.
Data from 47 ambulatory patients with MS who received ITB therapy were analyzed retrospectively. Outcome measures included Modified Ashworth Scale, Spasm Frequency Scale, Numeric Pain Rating Scale, and the Timed 25-Foot Walk. Repeated-measures ANOVA was used to test for changes in outcome measures between baseline and posttreatment (6 months and 1 year). Significance was set at p < 0.05. Descriptive data are expressed as the mean ± SD, and results of the repeated-measures ANOVA tests and the Wilcoxon rank-sum test are expressed as the mean ± SEM.
There was a statistically significant reduction in the following variables: 1) aggregate lower-extremity Modified Ashworth Scale scores (from 14.8 ± 1.0 before ITB therapy to 5.8 ± 0.8 at 6 months posttreatment and 6.4 ± 0.9 at 1 year [p < 0.05]); 2) Numeric Pain Rating Scale scores (4.4 ± 0.5 before ITB, 2.8 ± 0.5 at 6 months, and 2.4 ± 0.4 at 1 year [p < 0.05]); 3) spasm frequency (45.7% of the patients reported a spasm frequency of ≥ 1 event per hour before ITB therapy, whereas 15.6% and 4.3% of the patients reported the same at 6 months and 1 year posttreatment, respectively [p < 0.05]); and 4) the number of oral medications taken for spasticity (p < 0.05). Of the 47 patients, 34 remained ambulatory at 6 months, and 32 at 1 year posttreatment. There was no statistically significant change in performance on the Timed 25-Foot Walk test over time for those patients who remained ambulatory.
In this retrospective study, the authors found that ITB therapy is effective in reducing spasticity and related symptoms in ambulatory patients with MS. Because the use of ITB therapy is increasing in ambulatory patients with MS, randomized, prospective studies are important to help provide a more useful characterization of the effects of ITB therapy on ambulation.
Jianning Shao, Jaes Jones, Patrick Ellsworth, Ghaith Habboub, Gino Cioffi, Nirav Patil, Quinn T. Ostrom, Carol Kruchko, Jill S. Barnholtz-Sloan, Varun R. Kshettry, and Pablo F. Recinos
Spinal cord astrocytoma (SCA) is a rare tumor whose epidemiology has not been well defined. The authors utilized the Central Brain Tumor Registry of the United States (CBTRUS) to provide comprehensive up-to-date epidemiological data for this disease.
The CBTRUS was queried for SCAs on ICD-O-3 (International Classification of Diseases for Oncology, 3rd edition) histological and topographical codes. The age-adjusted incidence (AAI) per 100,000 persons was calculated and stratified by race, sex, age, and ethnicity. Joinpoint was used to calculate the annual percentage change (APC) in incidence.
Two thousand nine hundred sixty-nine SCAs were diagnosed in the US between 1995 and 2016, resulting in an average of approximately 136 SCAs annually. The overall AAI was 0.047 (95% CI 0.045–0.049), and there was a statistically significant increase from 0.051 in 1995 to 0.043 in 2016. The peak incidence of 0.064 (95% CI 0.060–0.067) was found in the 0- to 19-year age group. The incidence in males was 0.053 (95% CI 0.050–0.055), which was significantly greater than the incidence in females (0.041, 95% CI 0.039–0.044). SCA incidence was significantly lower both in patients of Asian/Pacific Islander race (AAI = 0.034, 95% CI 0.028–0.042, p = 0.00015) and in patients of Hispanic ethnicity (AAI = 0.035, 95% CI 0.031–0.039, p < 0.001). The incidence of WHO grade I SCAs was significantly higher than those of WHO grade II, III, or IV SCAs (p < 0.001).
The overall AAI of SCA from 1995 to 2016 was 0.047 per 100,000. The incidence peaked early in life for both sexes, reached a nadir between 20 and 34 years of age for males and between 35 and 44 years of age for females, and then slowly increased throughout adulthood, with a greater incidence in males. Pilocytic astrocytomas were the most common SCA in the study cohort. This study presents the most comprehensive epidemiological study of SCA incidence in the US to date.