Saman Shabani, Mayank Kaushal, Matthew Budde and Shekar N. Kurpad
Conventional MRI is routinely used to demonstrate the anatomical site of spinal cord injury (SCI). However, quantitative and qualitative imaging parameters have limited use in predicting neurological outcomes. Currently, there are no reliable neuroimaging biomarkers to predict short- and long-term outcome after SCI.
A prospective cohort of 23 patients with SCI (19 with cervical SCI [CSCI] and 4 with thoracic SCI [TSCI]) treated between 2007 and 2014 was included in the study. The American Spinal Injury Association (ASIA) score was determined at the time of arrival and at 1-year follow-up. Only 15 patients (12 with CSCI and 3 with TSCI) had 1-year follow-up. Whole-cord fractional anisotropy (FA) was determined at C1–2, following which C1–2 was divided into upper, middle, and lower segments and the corresponding FA value at each of these segments was calculated. Correlation analysis was performed between FA and ASIA score at time of arrival and 1-year follow-up.
Correlation analysis showed a positive but nonsignificant correlation (p = 0.095) between FA and ASIA score for all patients (CSCI and TCSI) at the time of arrival. Additional regression analysis consisting of only patients with CSCI showed a significant correlation (p = 0.008) between FA and ASIA score at time of arrival as well as at 1-year follow-up (p = 0.025). Furthermore, in case of patients with CSCI, a significant correlation between FA value at each of the segments (upper, middle, and lower) of C1–2 and ASIA score at time of arrival was found (p = 0.017, p = 0.015, and p = 0.002, respectively).
In patients with CSCI, the measurement of diffusion anisotropy of the high cervical cord (C1–2) correlates significantly with injury severity and long-term follow-up. However, this correlation is not seen in patients with TSCI. Therefore, FA can be used as an imaging biomarker for evaluating neural injury and monitoring recovery in patients with CSCI.
D. Ryan Ormond, Mohab Abozeid, Shekar Kurpad and Stephen J. Haines
William P. Van Wagenen pursued a research fellowship in Europe early in his career under the recommendation of Harvey Cushing. Later, Van Wagenen would be instrumental in the establishment of the William P. Van Wagenen Fellowship, a postgraduate fellowship for neurosurgeons from the AANS that requires study outside of a fellow’s country of residency training with plans to return to academic practice.
Since 1968, 54 Van Wagenen Fellowships have been awarded, sending 54 fellows from 31 institutions to 13 different countries. The academic productivity of fellows was studied to determine the academic “return on investment” of the fellowship.
Almost all fellows have spent some time in academic neurosurgery (94%), with the vast majority remaining in academics for their entire career (87%); 52% of fellows have received NIH funding, and 55% have been promoted to professor. The numbers are even more striking for the first half of Van Wagenen Fellows (who received the fellowship from its inception in 1968 to 1994) with at least 25 years of career development who remained in academics: 65% received NIH funding, 86% were promoted to professor, and 62% became chairs of academic departments. The Hirsch index of fellows, defined as h papers from an individual with at least h citations, is higher than the national mean and median values for academic neurosurgeons at every academic rank. Fellows have served on national committees and as AANS and CNS presidents and have given back financially to the Neurosurgery Research and Education Foundation (NREF) to fund future research activities of neurosurgical residents and young faculty.
The Van Wagenen Fellowship will continue to provide young neurosurgeons with opportunities to pursue novel research and network with peers internationally and to motivate young neurosurgeons to transform neurosurgery. The legacy of Cushing and Van Wagenen continues today through the Van Wagenen Fellowship, a legacy that will only continue to grow.
Ha Son Nguyen, Luyuan Li, Mohit Patel, Shekar Kurpad and Wade Mueller
The presence, extent, and distribution of intraventricular hemorrhage (IVH) have been associated with negative outcomes in aneurysmal subarachnoid hemorrhage (SAH). Several qualitative scores (Fisher grade, LeRoux score, and Graeb score) have been established for evaluating SAH and IVH. However, no study has assessed the radiodensity within the ventricular system in aneurysmal SAH patients with IVH. Prior studies have suggested that hemorrhage with a higher radiodensity, as measured by CT Hounsfield units, can cause more irritation to brain parenchyma. Therefore, the authors set out to investigate the relationship between the overall radiodensity of the ventricular system in aneurysmal SAH patients with IVH and their clinical outcome scores.
The authors reviewed the records of 101 patients who were admitted to their institution with aneurysmal SAH and IVH between January 2011 and July 2015. The following data were collected: age, sex, Glasgow Coma Scale (GCS) score, Hunt and Hess grade, extent of SAH (none, thin, or thick/localized), aneurysm location, and Glasgow Outcome Scale (GOS) score. To evaluate the ventricular radiodensity, the initial head CT scan was loaded into OsiriX MD. The ventricular system was manually selected as the region of interest (ROI) through all pertinent axial slices. After this, an averaged ventricular radiodensity was calculated from the ROI by the software. GOS scores were dichotomized as 1–3 and 4–5 subgroups for analysis.
On univariate analysis, younger age, higher GCS score, lower Hunt and Hess grade, and lower ventricular radiodensity significantly correlated with better GOS scores (all p < 0.05). Subsequent multivariate analysis yielded age (OR 0.936, 95% CI 0.895–0.979), GCS score (OR 3.422, 95% CI 1.9–6.164), and ventricular density (OR 0.937, 95% CI 0.878–0.999) as significant independent predictors (p < 0.05). A receiver operating characteristic curve yielded 12.7 HU (area under the curve 0.625, p = 0.032, sensitivity = 0.591, specificity = 0.596) as threshold between GOS scores of 1–3 and 4–5.
This study suggests that the ventricular radiodensity in aneurysmal SAH patients with IVH, along with GCS score and age, may serve as a predictor of clinical outcome.
Saman Shabani, Mayank Kaushal, Matthew Budde, Brian Schmit, Marjorie C. Wang and Shekar Kurpad
Cervical spondylotic myelopathy (CSM) is a common cause of spinal cord dysfunction. Recently, it has been shown that diffusion tensor imaging (DTI) may be a better biomarker than T2-weighted signal intensity (T2SI) on MRI for CSM. However, there is very little literature on a comparison between the quantitative measurements of DTI and T2SI in the CSM patient population to determine disease severity and recovery.
A prospective analysis of 46 patients with both preoperative DTI and T2-weighted MRI was undertaken. Normalized T2SI (NT2SI), regardless of the presence or absence of T2SI at the level of maximum compression (LMC), was determined by calculating the T2SI at the LMC/T2SI at the level of the foramen magnum. Regression analysis was performed to determine the relationship of fractional anisotropy (FA), a quantitative measure derived from DTI, and NT2SI individually as well their combination with baseline preoperative modified Japanese Orthopaedic Association (mJOA) score and ∆mJOA score at the 3-, 6-, 12-, and 24-month follow-ups. Goodness-of-fit analysis was done using residual diagnostics. In addition, mixed-effects regression analysis was used to evaluate the impact of FA and NT2SI individually. A p value < 0.05 was selected to indicate statistical significance.
Regression analysis showed a significant positive correlation between FA at the LMC and preoperative mJOA score (p = 0.041) but a significant negative correlation between FA at the LMC and the ΔmJOA score at the 12-month follow-up (p = 0.010). All other relationships between FA at the LMC and the baseline preoperative mJOA score or ∆mJOA score at the 3-, 6-, and 24-month follow-ups were not statistically significant. For NT2SI and the combination of FA and NT2SI, no significant relationships with preoperative mJOA score or ∆mJOA at 3, 6, and 24 months were seen on regression analysis. However, there was a significant correlation of combined FA and NT2SI with ∆mJOA score at the 12-month follow-up. Mixed-effects regression revealed that FA measured at the LMC was the only significant predictor of ΔmJOA score (p = 0.03), whereas NT2SI and time were not. Goodness-of-fit analysis did not show any evidence of lack of fit.
In this large prospective study of CSM patients, FA at LMC appears to be a better biomarker for determining long-term outcomes following surgery in CSM patients than NT2SI or the combination values at LMC.
Sanjay S. Dhall, Shekar N. Kurpad, R. John Hurlbert and Praveen V. Mummaneni
Saman Shabani, Mayank Kaushal, Matthew D. Budde, Marjorie C. Wang and Shekar N. Kurpad
Degenerative spondylotic myelopathy is the most common cause of spinal dysfunction, as well as nontraumatic spastic paraparesis and quadriparesis. Although conventional MRI is the gold standard for radiographic evaluation of the spinal cord, it has limited application for determining prognosis and recovery. In the last decade, diffusion tensor imaging (DTI), which is based on the property of preferential diffusion of water molecules, has gained popularity in evaluating patients with cervical spondylotic myelopathy (CSM). The use of DTI allows for evaluation of microstructural changes in the spinal cord not otherwise detected on routine conventional MRI. In this review, the authors describe the application of DTI in CSM evaluation and its role as an imaging biomarker to predict disease severity and prognosis.
Presented at the 2009 Joint Spine Section Meeting
Benjamin M. Ellingson, Brian D. Schmit and Shekar N. Kurpad
Using diffusion tensor MR imaging, the authors conducted a study to explore lesion growth and degeneration patterns, from the acute through chronic stages of spinal cord injury (SCI), in an experimental animal model.
In vivo and ex vivo diffusion tensor imaging was performed using a 9.4-T MR imaging system in rats allowed to recover from traumatic contusion SCI from 2 weeks through 25 weeks postinjury, mimicking progression of human SCI from the acute through chronic stages.
Results showed significant growth of the traumatic lesion up to 15 weeks postinjury, where both the size and mean diffusivity (MD) reached a maximum that was maintained through the remainder of recovery. Mean diffusivity was sensitive to overall spinal cord integrity, whereas fractional anisotropy showed specificity to sites of cavity formation. The use of an MD contour map for in vivo data and a 3D surface map for ex vivo data, showing MD as a function of rostral-caudal distance and recovery time, allowed documentation of rostral and caudal spreading of the lesion.
Results from this study demonstrate changes in both lesion morphology and diffusivity beyond previously reported time points and provide a unique perspective on the process of cavity formation and degeneration following traumatic SCI. Additionally, results suggest that MD more accurately defines regions of histological damage than do regions of T2 signal hyperintensity. This could have significant clinical implications in the detection and potential treatment of posttraumatic syringes in SCI.
Michael B. Jirjis, Chris Valdez, Aditya Vedantam, Brian D. Schmit and Shekar N. Kurpad
The aims of this study were to determine if the morphological and functional changes induced by neural stem cell (NSC) grafts after transplantation into the rodent spinal cord can be detected using MR diffusion tensor imaging (DTI) and, furthermore, if the DTI-derived mean diffusivity (MD) metric could be a biomarker for cell transplantation in spinal cord injury (SCI).
A spinal contusion was produced at the T-8 vertebral level in 40 Sprague Dawley rats that were separated into 4 groups, including a sham group (injury without NSC injection), NSC control group (injury with saline injection), co-injection control group (injury with Prograf), and the experimental group (injury with NSC and Prograf injection). The NSC injection was completed 1 week after injury into the site of injury and the rats in the experimental group were compared to the rats from the sham, NSC control, and co-injection groups. The DTI index, MD, was assessed in vivo at 2, 5, and 10 weeks and ex vivo at 10 weeks postinjury on a 9.4-T Bruker scanner using a spin-echo imaging sequence. DTI data of the cervical spinal cord from the sham surgery, injury with saline injection, injury with injection of Prograf only, and injury with C17.2 NSC and Prograf injection were examined to evaluate if cellular proliferation induced by intrathoracic C17.2 engraftment was detectable in a noninvasive manner.
At 5 weeks after injury, the average fractional anisotropy, longitudinal diffusion (LD) and radial diffusion (RD) coefficients, and MD of water (average of the RD and LD eigenvalues in the stem cell line–treated group) increased to an average of 1.44 × 10−3 sec/mm2 in the cervical segments, while the control groups averaged 0.98 × 10−3 s/mm2. Post hoc Tukey's honest significant difference tests demonstrated that the transplanted stem cells had significantly higher MD values than the other groups (p = 0.032 at 5 weeks). In vivo and ex vivo findings at 10 weeks displayed similar results. This statistical difference between the stem cell line and the other groups was maintained at the 10-week postinjury in vivo and ex vivo time points.
These results indicate that the DTI-derived MD metric collected from noninvasive imaging techniques may provide useful biomarker indices for transplantation interventions that produce changes in the spinal cord structure and function. Though promising, the results demonstrated here suggest additional work is needed before implementation in a clinical setting.
Zoher Ghogawala, Shekar Kurpad, Asdrubal Falavigna, Michael W. Groff, Daniel M. Sciubba, Jau-Ching Wu, Paul Park, Sigurd Berven, Daniel J. Hoh, Erica F. Bisson, Michael P. Steinmetz, Marjorie C. Wang, Dean Chou, Charles A. Sansur, Justin S. Smith and Luis M. Tumialán