Melissa M. Stamates, David M. Frim, Carina W. Yang, Gregory L. Katzman and Saad Ali
Tethered cord syndrome (TCS) is a neurosurgical disorder with varied clinical manifestations believed to result from vascular compromise due to stretch forces on the spinal cord. Conventional supine MRI findings may include a low-lying conus medullaris, thickened or fat-infiltrated filum terminale, or lipoma; however, imaging sensitivity and specificity for tethered cord can be low. The purpose of this study was to evaluate the utility of prone MRI in the diagnosis of tethered and retethered spinal cord.
Medical records were reviewed in 41 patients who underwent surgical release of tethered cord and in whom preoperative prone MRI sequences were available. Patients were divided into Group 1 (new TCS diagnosis) and Group 2 (recurrent TCS after previous untethering). Absolute conus ventral motion and motion as a percentage of canal width between supine and prone positions was measured in these 2 groups via sagittal T2-weighted sequences; these groups were compared with 30 consecutive patients (Group 3) who were classified as the normal control group.
The mean ventral motion was as follows: Group 1 (absolute: 0.5 ± 0.5 mm [range 0–2.4 mm]; canal percentage: 3.7% ± 3.9% [range 0%–16.3%]); Group 2 (absolute: 0.4 ± 0.7 mm [range 0–2.6 mm]; canal percentage: 2.2% ± 3.7% [range 0%–14.0%]); and Group 3 (absolute: 3.4 ± 1.3 mm [range 1.4–5.6 mm]; canal percentage: 22.0% ± 7.2% [range 10.5%–36.1%]). Whereas 38/41 surgically treated patients with TCS had diminished (< 10% canal width) ventral motion on preoperative MRI, 30/30 controls had > 10% canal width motion. Sensitivity and specificity were thereby calculated as 92.7% and 100%, respectively.
In the present series, prone imaging is found to be a sensitive and specific tool, and the authors believe it may have a role as supportive evidence in the diagnosis of tethered and retethered spinal cord.
Ali Nourbakhsh, Jinping Yang, Sean Gallagher, Anil Nanda, Prasad Vannemreddy and Kim J. Garges
The purpose of this study was to find a landmark according to which the surgeon can dissect the cervical spine safely, with the lowest possibility of damaging the vertebral artery (VA) during anterior approaches to the cervical spine or the VA.
The “safe zone” for each level of the cervical spine was described as an area where the surgeon can start from the midline in that zone and dissect the soft tissue laterally to end up on the transverse process and cross the VA while still on the transverse process. In other words, safe zone signifies the narrowest width of the transverse process at each level. In such an approach, the VA is protected from the inadvertent deep penetration of the instruments by the transverse process. The surgical safe zone for each level was the common area among at least 95% of the safe zones for that level. For the purpose of defining the upper and lower borders of the safe zone for each level, the line passing from the upper vertebral border perpendicular to the midline (upper vertebral border line) was used as a reference.
Cervical spines of 64 formalin-fixed cadavers were dissected. The soft tissue in front of the transverse process and intertransverse space was removed. Digital pictures of the specimens were taken before and after removal of the transverse processes, and the distance to the upper and lower border of the safe zone from the upper vertebral border line was measured on the digital pictures with Image J software. The VA diameter and distance from the midline at each level were also measured. To compare the means, the authors used t-test and ANOVA.
The surgical safe zone lies between 1 mm above and 1 mm below the upper vertebral border at the fourth vertebra, 2 mm above and 1 mm below the upper vertebral border at the fifth vertebra, and 1 mm above and 2 mm below the upper vertebral border of the sixth vertebra. The VA was observed to be tortuous in 13% of the intertransverse spaces. There is a positive association between disc degeneration and tortuosity of the VA at each level (p < 0.001). The artery becomes closer to the midline (p < 0.001) and moves posteriorly during its ascent.
Dissection of the soft tissue off the bone along the surgical safe zone and removal of the transverse process afterward can be a practical and safe approach to avoid artery lacerations. The findings in the present study can be used in anterior approaches to the cervical spine, especially when the tortuosity of the artery mandates exposure of the VA prior to uncinate process resection, tumor excision, or VA repair.
Alexander Ivanov, Andreas Linninger, Chih-Yang Hsu, Sepideh Amin-Hanjani, Victor A. Aletich, Fady T. Charbel and Ali Alaraj
The use of digital subtraction angiography (DSA) for semiquantitative cerebral blood flow(CBF) assessment is a new technique. The aim of this study was to determine whether patients with aneurysmal subarachnoid hemorrhage (aSAH) with higher Hunt and Hess grades also had higher angiographic contrast transit times (TTs) than patients with lower grades.
A cohort of 30 patients with aSAH and 10 patients without aSAH was included. Relevant clinical information was collected. A method to measure DSA TTs by color-coding reconstructions from DSA contrast-intensity images was applied. Regions of interest (ROIs) were chosen over major cerebral vessels. The estimated TTs included time-to-peak from 0% to 100% (TTP0–100), TTP from 25% to 100% (TTP25–100), and TT from 100% to 10% (TT100–10) contrast intensities. Statistical analysis was used to compare TTs between Group A (Hunt and Hess Grade I-II), Group B (Hunt and Hess Grade III-IV), and the control group. The correlation coefficient was calculated between different ROIs in aSAH groups.
There was no difference in demographic factors between Group A (n = 10), Group B (n = 20), and the control group (n = 10). There was a strong correlation in all TTs between ROIs in the middle cerebral artery (M1, M2) and anterior cerebral artery (A1, A2). There was a statistically significant difference between Groups A and B in all TT parameters for ROIs. TT100–10 values in the control group were significantly lower than the values in Group B.
The DSA TTs showed significant correlation with Hunt and Hess grades. TT delays appear to be independent of increased intracranial pressure and may be an indicator of decreased CBF in patients with a higher Hunt and Hess grade. This method may serve as an indirect technique to assess relative CBF in the angiography suite.
Anuj Singla, Scott Yang, Brian C. Werner, Jourdan M. Cancienne, Ali Nourbakhsh, Adam L. Shimer, Hamid Hassanzadeh and Francis H. Shen
Lumbar epidural steroid injections (LESIs) are performed for both diagnostic and therapeutic purposes for a variety of indications, including low-back pain, the leading cause of disability and expense due to work-related conditions in the US. The steroid agent used in epidural injections is reported to relieve nerve root inflammation, local ischemia, and resultant pain, but the injection may also have an adverse impact on spinal surgery performed thereafter. In particular, the possibility that preoperative epidural injections may increase the risk of surgical site infection after lumbar spinal fusion has been reported but has not been studied in detail. The goal of the present study was to use a large national insurance database to analyze the association of preoperative LESIs with surgical site infection after lumbar spinal fusion.
A nationwide insurance database of patient records was used for this retrospective analysis. Current Procedural Terminology codes were used to query the database for patients who had undergone LESI and 1- or 2-level lumbar posterior spinal fusion procedures. The rate of postoperative infection after 1- or 2-level posterior spinal fusion was analyzed. These study patients were then divided into 3 separate cohorts: 1) lumbar spinal fusion performed within 1 month after LESI, 2) fusion performed between 1 and 3 months after LESI, and 3) fusion performed between 3 and 6 months after LESI. The study patients were compared with a control cohort of patients who underwent lumbar fusion without previous LESI.
The overall 3-month infection rate after lumbar spinal fusion procedure was 1.6% (1411 of 88,540 patients). The infection risk increased in patients who received LESI within 1 month (OR 2.6, p < 0.0001) or 1–3 months (OR 1.4, p = 0.0002) prior to surgery compared with controls. The infection risk was not significantly different from controls in patients who underwent lumbar fusion more than 3 months after LESI.
Lumbar spinal fusion performed within 3 months after LESI may be associated with an increased rate of postoperative infection. This association was not found when lumbar fusion was performed more than 3 months after LESI.
Hua-Jun Zhou, Tao Tang, Han-Jin Cui, A-Li Yang, Jie-Kun Luo, Yuan Lin, Qi-Dong Yang and Xing-Qun Li
Angiogenesis occurs after intracerebral hemorrhage (ICH). Thrombin mediates mitogenesis and survival in endothelial cells and induces angiogenesis. The present study aimed to clarify whether thrombin is involved in triggering ICH-related angiogenesis.
In the first part of the experiment, autologous blood (with or without hirudin) was injected to induce ICH. In the second part, rats received either 1 U (50 μl) thrombin or 50 μl 0.9% sterile saline. In both parts, 5-bromo-2-deoxyuridine (BrdU) was administered intraperitoneally. Brains were perfused to identify BrdU-positive/von Willebrand factor (vWF)–positive nuclei. The expression of hypoxia-inducible factor–1α (HIF-1α), vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and Ang-2 was evaluated by immunohistochemistry and quantitative real-time reverse transcription polymerase chain reaction.
After ICH, the number of BrdU-/vWF-positive nuclei increased until Day 14, and vessels positive for HIF-1α, VEGF, Ang-1, and Ang-2 were observed around the clot. Quantitative analysis showed that ICH upregulated expression of HIF-1α, VEGF, Ang-1, and Ang-2 notably compared with that in sham controls (p < 0.05). However, hirudin significantly inhibited these effects. After thrombin treatment, many BrdU-positive/vWF-positive nuclei and HIF-1α–, VEGF-, Ang-1– and Ang-2–positive vessels could be detected around the affected region.
Thrombin can induce angiogenesis in rat brains and may be an important trigger for ICH-related angiogenesis.
Hanjin Cui, Ali Yang, Huajun Zhou, Yang Wang, Jiekun Luo, Jun Zhou, Tao Liu, Pengfei Li, Jing Zhou, En Hu, Zehui He, Wang Hu and Tao Tang
Thrombin is a unique factor that triggers post-intracerebral hemorrhage (ICH) angiogenesis by increasing hypoxia-inducible factor–1α (HIF-1α) at the protein level. However, HIF-1α mRNA remains unchanged. MicroRNAs (miRNAs) mediate posttranscriptional regulation by suppressing protein translation from mRNAs. This study aimed to determine if miRNAs might be involved in thrombin-induced angiogenesis after ICH by targeting HIF-1α or its upstream prolyl hydroxylase domains (PHDs).
The study was divided into two parts. In part 1, rats received an injection of thrombin into the right globus pallidus. An miRNA array combined with miRNA target prediction, luciferase activity assay, and miRNA mimic/inhibitor transfection were used to identify candidate miRNAs and target genes. Part 2 included experiments 1 and 2. In experiment 1, rats were randomly divided into the sham group, ICH group, and ICH+hirudin–treated (thrombin inhibitor) group. In experiment 2, the rats were randomly divided into the sham group, ICH group, ICH+antagomir group, ICH+antagomir-control group, and ICH+vehicle group. Western blotting and quantitative real-time polymerase chain reaction were used to determine the expression of protein and miRNA, respectively. The coexpression of miR-24–1-5p (abbreviated to miR-24) and von Willebrand factor was detected by in situ hybridization and immunohistochemical analysis. The angiogenesis was evaluated by double-labeling immunofluorescence. Neurological function was evaluated by body weight, modified Neurological Severity Scores, and corner turn and foot-fault tests.
In part 1, it was shown that miR-24, which is predicted to target PHD1, was upregulated (fold-change of 1.83) after thrombin infusion, and that the miR-24 mimic transfection decreased luciferase activity and downregulated PHD1 expression (p < 0.05). miR-24 inhibitor transfection increased PHD1 expression (p < 0.05). In part 2, it was shown that miR-24 was expressed in endothelial cells. The HIF-1α protein level and proliferating cell nuclear antigen–positive (PCNA+) nuclei in vessels were increased, while the PHD1 protein level was decreased after ICH, and these effects were reversed by hirudin (p < 0.05). The antagomiR-24–treated rats exhibited a markedly lower body weight and significantly poorer recovery from neurological deficit compared with those in ICH groups (p < 0.05). AntagomiR-24 intervention also led to lower miR-24 expression, a higher PHD1 protein level, and fewer PCNA+ nuclei in vessels compared with those in ICH groups (p < 0.05).
The present study suggests that thrombin reduces HIF-1α degradation and initiates angiogenesis by increasing miR-24, which targets PHD1 after ICH.
Jian-Hua Zhong, Hua-Jun Zhou, Tao Tang, Han-Jin Cui, A-Li Yang, Qi-Mei Zhang, Jing-Hua Zhou, Qiang Zhang, Xun Gong, Zhao-Hui Zhang and Zhi-Gang Mei
Reactive astrogliosis, a key feature that is characterized by glial proliferation, has been observed in rat brains after intracerebral hemorrhage (ICH). However, the mechanisms that control reactive astrogliosis formation remain unknown. Notch-1 signaling plays a critical role in modulating reactive astrogliosis. The purpose of this paper was to establish whether Notch-1 signaling is involved in reactive astrogliosis after ICH.
ICH was induced in adult male Sprague-Dawley rats via stereotactic injection of autologous blood into the right globus pallidus. N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT) was injected into the lateral ventricle to block Notch-1 signaling. The rats’ brains were perfused to identify proliferating cell nuclear antigen (PCNA)-positive/GFAP-positive nuclei. The expression of GFAP, Notch-1, and the activated form of Notch-1 (Notch intracellular domain [NICD]) and its ligand Jagged-1 was assessed using immunohistochemical and Western blot analyses, respectively.
Notch-1 signaling was upregulated and activated after ICH as confirmed by an increase in the expression of Notch-1 and NICD and its ligand Jagged-1. Remarkably, blockade of Notch-1 signaling with the specific inhibitor DAPT suppressed astrocytic proliferation and GFAP levels caused by ICH. In addition, DAPT improved neurological outcome after ICH.
Notch-1 signaling is a critical regulator of ICH-induced reactive astrogliosis, and its blockage may be a potential therapeutic strategy for hemorrhagic injury.
Phoenix, Arizona • March 6–9, 2013
2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010