Yu-Feng Su

Outcome analyses of interbody titanium cage fusion used in the anterior discectomy for cervical degenerative disc disease.

Anterior discectomy and fusion to treat cervical degenerative disc disease is the preferred procedure for many spine surgeons. The ideal device for structural reconstruction of the anterior cervical spine remains controversial. The purpose of this prospective study was to investigate the effectiveness of a non-threaded titanium cage in performing anterior spinal fusion for cervical degenerative disc disease. The clinical and radiologic data of 78 consecutive patients were reviewed. Neurologic outcome was assessed using Odoms criteria. Neck pain was graded using a 10-point visual analog scale. The cervical spinal curvature, the height of foramina, and fusion status were evaluated on preoperative and postoperative radiographs. Mean follow-up was 24.9 (range 18-35) months. An excellent or good result was found in 92% of the patients with radiculopathy, 69% of those with myelopathy, and 73% of those with myeloradiculopathy. Statistical analyses also showed improvement of cervical pain after surgery (P < 0.001) and a significant increase in foraminal height (P = 0.035). Cervical kyphosis was present in 27 (34%) patients before surgery; it was corrected to lordosis in 9. The fusion rate at 12 months and 24 months was 91% and 95%, respectively. No surgery or cage-related complication occurred in these patients. Non-threaded interbody cage fusion in this study achieved a high fusion rate and had a good neurologic outcome. These results suggest that non-threaded cage fusion is a safe and effective method for anterior cervical discectomy.

Effect of Aspirin and Indomethacin on Prostaglandin E2 Synthesis in C6 Glioma Cells

Prostaglandin E2 (PGE2) plays an important role in immunosuppression and tumor growth. PGE2 inhibitors such as aspirin and indomethacin suppress experimental tumor growth. Little is known of the relationship between PGE2 synthesis in brain tumors and the dose of aspirin or indomethacin. The present study was undertaken to evaluate the effect of different doses of aspirin and indomethacin on PGE2 synthesis in C6 glioma cells. C6 glioma cells were incubated with different concentrations (2, 4, and 8 μM) of aspirin and indomethacin for 1, 2, 4, 6, 8, 12, and 24 hours. Intracellular PGE2 concentration was measured by enzyme immunoassay. Each concentration of aspirin and indomethacin effectively inhibited PGE2 synthesis. Concentrations of 2, 4, and 8 μM of aspirin significantly inhibited PGE2 production at 6, 4, and 1 hours, respectively, and the inhibition persisted for more than 24 hours (p < 0.05). Concentrations of 2 and 4 μM of indomethacin were effective at 4 and 2 hours (p < 0.05), respectively. However, inhibition was not observed beyond 12 hours (p > 0.05). Indomethacin 8 μM was effective at 1 hour and the inhibition persisted beyond 24 hours (p < 0.05). Our study demonstrates that aspirin and indomethacin inhibit PGE2 synthesis in C6 glioma cells and that low‐dose aspirin is as effective as high‐dose aspirin. This study may encourage future clinical use of low‐dose aspirin in the prevention or treatment of brain tumors.

Assessing the Intraoperative Accuracy of Pedicle Screw Placement by Using a Bone-Mounted Miniature Robot System through Secondary Registration.

Introduction Pedicle screws are commonly employed to restore spinal stability and correct deformities. The Renaissance robotic system was developed to improve the accuracy of pedicle screw placement. Purpose In this study, we developed an intraoperative classification system for evaluating the accuracy of pedicle screw placements through secondary registration. Furthermore, we evaluated the benefits of using the Renaissance robotic system in pedicle screw placement and postoperative evaluations. Finally, we examined the factors affecting the accuracy of pedicle screw implantation. Results Through use of the Renaissance robotic system, the accuracy of Kirschner-wire (K-wire) placements deviating <3 mm from the planned trajectory was determined to be 98.74%. According to our classification system, the robot-guided pedicle screw implantation attained an accuracy of 94.00% before repositioning and 98.74% after repositioning. However, the malposition rate before repositioning was 5.99%; among these placements, 4.73% were immediately repositioned using the robot system and 1.26% were manually repositioned after a failed robot repositioning attempt. Most K-wire entry points deviated caudally and laterally. Conclusion The Renaissance robotic system offers high accuracy in pedicle screw placement. Secondary registration improves the accuracy through increasing the precision of the positioning; moreover, intraoperative evaluation enables immediate repositioning. Furthermore, the K-wire tends to deviate caudally and laterally from the entry point because of skiving, which is characteristic of robot-assisted pedicle screw placement.

Attenuation of subarachnoid hemorrhage-induced apoptotic cell death with 17 beta-estradiol. Laboratory investigation.

OBJECT Apoptosis is implicated in vasospasm and long-term sequelae of subarachnoid hemorrhage (SAH). The authors observed that 17beta-estradiol (E2) can attenuate cerebral vasospasm, lower endothelin-1 production, and preserve normal endothelial nitric oxide synthase expression by reduction of inducible NO synthase expression in experimental SAH. The authors investigated the potential antiapoptotic effects of E2 in an experimental rat model of SAH. METHODS The authors examined the antiapoptotic effects of E2 in a double-hemorrhage SAH model in male Sprague-Dawley rats. The rats underwent subcutaneous implantation of a Silastic tube containing corn oil either with or without E2, and some E2-treated animals also received ICI 182,780 (a nonselective estrogen receptor [ER] antagonist) for 7 days after SAH. The degree of vasospasm was determined by averaging the cross-sectional areas of the basilar artery 7 days after SAH. The expression of apoptotic indicators, including TNF-alpha, caspase 3, Bcl-2, Bax, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL), and cell death assays were used for detection of apoptosis. RESULTS Treatment with E2 significantly attenuated SAH-induced vasospasm. Seven days after the induction of SAH, positive TUNEL-staining was seen, and DNA fragmentation was increased in the dentate gyrus. Increased TNF-alpha and cleaved caspase-3 protein expression and decreased Bcl-2 protein expression in the dentate gyrus were also observed. These changes were reversed with E2-treatment but not in the presence of ICI 182,780. However, the expression of Bax did not change after SAH either with or without E2 treatment. CONCLUSIONS The authors found that E2 appears to confer an antiapoptotic effect that reduces secondary brain injury after SAH via estrogen receptor-dependent mechanisms. This finding provides support for possible future applications of E2 treatment for the reduction of secondary injury after SAH in patients.

The effect of an adenosine A1 receptor agonist in the treatment of experimental subarachnoid hemorrhage-induced cerebrovasospasm

SummaryBackground. Adenosine is a potent vasodilator and an important modulator of cardiovascular function. It has been postulated that nitric oxide (NO) is involved in adenosine-induced vasodilation. This study was designed to examine the effect of an adenosine A1 agonist, N6-cyclopentyladenosine (CPA), in the prevention of subarachnoid haemorrhage (SAH)-induced vasospasm. Method. Experimental SAH was induced in Sprague-Dawley rats by injecting 0.3 mL autogenous blood into the cisterna magna. Intraperitoneal injections of CPA (0.003 mg/kg), or vehicle were administered 5 min and 24 hours after induction of SAH. The degree of vasospasm was determined by averaging the cross sectional areas of the basilar artery 2 days after SAH. Expressions of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in basilar artery were evaluated. Findings. There were no significant differences among the control and treated groups in physiological parameters recorded before sacrifice. When compared with animals in the control group, cross-sectional area of basilar arteries areas in the SAH only, SAH plus vehicle and SAH plus CPA groups were reduced by 19% (p < 0.01), 22% (p < 0.01), and 9% (p = 0.133), respectively. The cross-sectional areas of the CPA-treated group differed significantly from those of the SAH only and SAH plus vehicle group (p < 0.05). Induction of iNOS-mRNA and protein in basilar artery by SAH was not significantly diminished by CPA. The SAH-induced suppression of eNOS-mRNA and protein were relieved by CPA treatment. Conclusions. This is the first evidence to show an adenosine A1 receptor agonist is effective in partially preventing SAH-induced vasospasm without significant cardiovascular complications. The mechanisms of adenosine A1 receptor agonists in attenuating SAH-induced vasospasm may be, in part, related to preserve the normal eNOS expression after SAH. Inability in reversing the increased iNOS expression after SAH may lead to the incomplete anti-spastic effect of CPA.

Progesterone attenuates experimental subarachnoid hemorrhage-induced vasospasm by upregulation of endothelial nitric oxide synthase via Akt signaling pathway.

Cerebral vasospasm is the leading cause of mortality and morbidity in patients after aneurysmal subarachnoid hemorrhage (SAH). However, the mechanism and adequate treatment of vasospasm are still elusive. In the present study, we evaluate the effect and possible mechanism of progesterone on SAH-induced vasospasm in a two-hemorrhage rodent model of SAH. Progesterone (8 mg/kg) was subcutaneously injected in ovariectomized female Sprague-Dawley rats one hour after SAH induction. The degree of vasospasm was determined by averaging the cross-sectional areas of basilar artery 7 days after first SAH. Expressions of endothelial nitric oxide synthase (eNOS) and phosphorylated Akt (phospho-Akt) in basilar arteries were evaluated. Prior to perfusion fixation, there were no significant differences among the control and treated groups in physiological parameters recorded. Progesterone treatment significantly (P < 0.01) attenuated SAH-induced vasospasm. The SAH-induced suppression of eNOS protein and phospho-Akt were relieved by progesterone treatment. This result further confirmed that progesterone is effective in preventing SAH-induced vasospasm. The beneficial effect of progesterone might be in part related to upregulation of expression of eNOS via Akt signaling pathway after SAH. Progesterone holds therapeutic promise in the treatment of cerebral vasospasm following SAH.

17β-Estradiol attenuates secondary injury through activation of Akt signaling via estrogen receptor alpha in rat brain following subarachnoid hemorrhage

BACKGROUND Apoptosis is implicated in vasospasm and the long-term sequelae of subarachnoid hemorrhage (SAH). This study tested the hypothesis that attenuation of SAH-induced apoptosis after 17β-estradiol (E2) treatment is associated with an increase in phosphorylation of Akt via estrogen receptor-α (ER-α) in rats. MATERIALS AND METHODS We examined the expression of phospho-Akt, ERα and ERβ, and apoptosis in cerebral cortex, hippocampus, and dentate gyrus in a two-hemorrhage SAH model in rats. We subcutaneously implanted other rats with a silicone rubber tube containing E2; they received daily injections of nonselective estrogen receptor antagonist (ICI 182,780), selective ERα-selective antagonist (methyl-piperidino-pyrazole), or ERβ-selective antagonist (R,R-tetrahydrochrysene) after the first hemorrhage. RESULTS At 7 d after the first SAH, protein levels of phospho-Akt and ERα were significantly decreased and caspase-3 was significantly increased in the dentate gyrus. The cell death assay revealed that DNA fragmentation was significantly increased in the dentate gyrus. Those actions were reversed by E2 and blocked by ICI 182,780 and methyl-piperidino-pyrazole, but not R,R-tetrahydrochrysene. However, there were no significant changes in the expression of the protein levels of phospho-Akt, ERα, ERβ, and caspase-3, and DNA fragmentation after SAH. CONCLUSIONS The present study shows that a beneficial effect of E2 in attenuating SAH-induced apoptosis is associated with activation of the expression of phospho-Akt and ERα, and alteration in caspase-3 protein expression via an ERα-dependent mechanism in the dentate gyrus. These data support further the investigation of E2 in the treatment of SAH in humans.

Plasma levels of transforming growth factor-beta 1 before and after removal of low- and high-grade astrocytomas.

Transforming growth factor-beta 1 (TGF-β1) has been reported to be a possible marker for a number of tumors, including brain tumors. The aim of this study was to measure the plasma levels of TGF-β1 in patients with low- and high-grade astrocytomas before and after surgery. This prospective study included 14 patients with low-grade astrocytomas and 25 with high-grade astrocytomas who underwent tumor removal and 13 controls (patients who underwent cranioplasty for skull bone defects). Plasma levels of TGF-β1 were measured in all subjects using enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis showed that when the level of TGF-β1 before tumor removal was ≥ 2.52 ng/ml, astrocytoma was predicted with a sensitivity of 94.9% and specificity of 100%. The mean plasma level of TGF-β1 in both the low-grade and high-grade astrocytoma groups significantly decreased after tumor removal (p<0.05); there was no significant change in TGF-β1 plasma level of the controls following surgery. Patients with high-grade astrocytomas had a significantly higher mortality rate than patients with low-grade astrocytomas (p=0.019) and significantly shorter survival (p=0.008). A positive correlation between TGF-β1 level after tumor removal and tumor volume was only found in the high-grade astrocytoma group (γ=0.597, p=0.002). The findings show that plasma TGF-β1 level was increased in patients with low-grade and high-grade astrocytoma, and that the levels significantly decreased after tumor removal in both groups. The results provide additional evidence that TGF-β1 might be useful as a tumor marker for astrocytomas.

Prevention and reversal of vasospasm and ultrastructural changes in basilar artery by continuous infusion of CGS 35066 following subarachnoid hemorrhage.

Endothelin-1, a potent vasoconstrictive peptide, has been implicated in the pathogenesis of cerebral vasospasm following subarachnoid hemorrhage (SAH). The goal of this study was to evaluate the effect of continuous intravenous infusion of a highly selective endothelin-converting enzyme-1 inhibitor, CGS 35066, on the prevention and reversal of cerebral vasospasm following SAH. New Zealand white rabbits were subjected to SAH by injecting autologous arterial blood into the cisterna magna. Infusion of CGS 35066 at dosages of 1, 3, or 10 mg/kg/ day was initiated either 1 hr and 24 hrs later in the prevention and reversal protocols, respectively. Animals were sacrificed by perfusion-fixation 48 hrs after SAH induction. The cross-sectional areas of basilar arteries were measured using computer-assisted videomicroscopy. Ultrastructural changes in basilar arteries were determined using electron microscopy. CGS 35066 significantly prevented and reversed the arterial narrowing after SAH in all three groups. The mean cross-sectional areas of arteries from animals in both the prevention and reversal protocol groups that received 10 mg/kg/day of CGS 35066 did not differ significantly from those of the healthy controls. Histological studies of the basilar artery in the 10 mg/kg/day treatment group did not show pathomorphological changes, such as corrugation of the endothelium seen at 2 days after SAH induction or vacuole formation in the endothelial cells noted in the vehicle-treated SAH group. These findings suggest that CGS 35066 is a promising therapeutic agent for the prevention and reversal of cerebral vasospasm after SAH. It also prevents the pathological changes in vascular walls due to SAH.

Giant nondural-based cauda equina meningioma with multiple cysts

SummaryA very rare case of a giant nondural-based cauda equina meningioma with multiple cysts was presented. Spinal meningioma most commonly occurs in the thoracic or cervical region and typically adheres to the dura. Only six cases of nondural-based meningioma have been reported in English literature. All occurred in the cauda equina region. These patients were predominantly female and younger than those with typical intraspinal meningioma.A 46-year-old woman had a 4-year history of lower back pain and right leg pain. Progressive weakness of both lower extremities occurred. Magnetic resonance imaging revealed a giant cauda equina tumor with multiple cysts from T12 to L4. Following laminectomies from T11 to L5 and intradural exposure, the tumor was found to be draped loosely by the roots of the cauda equina and attached to a root without any firm connection with dura mater. Complete removal of the tumor was achieved after microdissection of arachnoid and sacrifice of an involved rootlet of the cauda equina. The appearance of tumor was that of a typical neurilemmoma. However, histological and immunohistochemical analyses were consistent with meningioma.Nondural-based intraspinal meningiomas are very rare, particularly a giant tumor with multiple cysts as our presenting case. All of the cases previously reported, including our case, have been located in the cauda equina region. Most of the patients were female and were young, suggesting that the nondural-based cauda equina meningiomas are age- and sex-related. An accurate preoperative and operative diagnosis are difficult. Care must be taken in the management of cauda equina tumors resembling neurilemmoma which may in fact represent meningioma, particularly in the younger female.