The Impact of Enteral Nimodipine on Endothelial Cell Apoptosis in an Animal Subarachnoid Hemorrhage Model.

BACKGROUND: Enteral nimodipine is the most evidence-based and widely used drug for the treatment of delayed cerebral ischemia and is known to have various neuroprotective functions. However, the neuroprotective mechanism of nimodipine still remains unclear, and the effects of nimodipine remain ambiguous. Herein, we studied the effect of enteral nimodipine on endothelial apoptosis after subarachnoid hemorrhage (SAH). METHODS: SAH was experimentally introduced in white rabbits (n = 42) that were grouped as follows: enteral nimodipine (SAH-nimodipine group, n = 14), a control that received normal saline (SAH-saline group, n = 13), and a control without hemorrhage (control group, n = 15). On the third day after SAH induction, the brain stem, including the vertebrobasilar vascular system, was extracted. The effects of enteral nimodipine were analyzed by group using histopathologic analysis, including immunohistochemical staining of apoptosis-related proteins (Bcl2 [anti-apoptotic] and Bax [pro-apoptotic]). RESULTS: Cytoplasmic vacuolation of smooth muscle cells was observed in two SAH hemorrhagic groups and was more prominent in the SAH-saline group. Endothelial desquamation was observed only in the SAH-saline group. For the basilar artery, expression of Bcl2 and Bax in the SAH-nimodipine group was lower than that in the SAH-saline group, but significant differences were not observed (pBcl2 = 0.311 and pBax = 0.720, respectively). In penetrated arterioles, the expression of Bax in the SAH-nimodipine group was significantly lower than that of the SAH-saline group (p < 0.001). The thickness of the tunica media in the basilar artery was thinner in the SAH-nimodipine group than in the SAH-saline group (p < 0.001). CONCLUSIONS: This study suggests that enteral nimodipine may have a neuroprotective function by inhibiting endothelial apoptosis in small arterioles and preventing smooth muscle cell proliferation in large arteries.

The iterative implementation of a comprehensive enhanced recovery after surgery protocol in all spinal surgery in Korea: a comparative analysis of clinical outcomes and medical costs between primary spinal tumors and degenerative spinal diseases.

OBJECTIVE: Most studies on the enhanced recovery after surgery (ERAS) protocol in spine surgery have focused on patients with degenerative spinal diseases (DSDs), resulting in a lack of evidence for a comprehensive ERAS protocol applicable to patients with primary spine tumors (PSTs) and other spinal diseases. The authors had developed and gradually adopted components of the comprehensive ERAS protocol for all spine surgical procedures from 2003 to 2011, and then the current ERAS protocol was fully implemented in 2012. This study aimed to evaluate the impact and the applicability of the comprehensive ERAS protocol across all spine surgical procedures and to compare outcomes between the PST and DSD groups. METHODS: Adult spine surgical procedures were conducted from 2003 to 2021 at the Seoul National University Hospital Spine Center and data were retrospectively reviewed. The author divided the study periods into the developing ERAS (2003-2011) and post-current ERAS (2012-2021) periods, and outcomes were compared between the two periods. Surgical procedures for metastatic cancer, infection, and trauma were excluded. Interrupted time series analysis (ITSA) was used to assess the impact of the ERAS protocol on medical costs and clinical outcomes, including length of stay (LOS) and rates of 30-day readmission, reoperation, and surgical site infection (SSI). Subgroup analyses were conducted on the PST and DSD groups in terms of LOS and medical costs. RESULTS: The study included 7143 surgical procedures, comprising 1494 for PSTs, 5340 for DSDs, and 309 for other spinal diseases. After ERAS protocol implementation, spine surgical procedures showed significant reductions in LOS and medical costs by 22% (p = 0.008) and 22% (p < 0.001), respectively. The DSD group demonstrated a 16% (p < 0.001) reduction in LOS, whereas the PST group achieved a 28% (p < 0.001) reduction, noting a more pronounced LOS reduction in PST surgical procedures (p = 0.003). Medical costs decreased by 23% (p < 0.001) in the DSD group and 12% (p = 0.054) in the PST group, with a larger cost reduction for DSD surgical procedures (p = 0.021). No statistically significant differences were found in the rates of 30-day readmission, reoperation, and SSI between the developing and post-current ERAS implementation periods (p = 0.65, p = 0.59, and p = 0.52, respectively). CONCLUSIONS: Comprehensive ERAS protocol implementation significantly reduced LOS and medical costs in all spine surgical procedures, while maintaining comparable 30-day readmission, reoperation, and SSI rates. These findings suggest that the ERAS protocol is equally applicable to all spine surgical procedures, with a more pronounced effect on reducing LOS in the PST group and on reducing medical costs in the DSD group.

Cervical kinematic change after posterior full-endoscopic cervical foraminotomy for disc herniation or foraminal stenosis.

OBJECTIVE: Posterior full-endoscopic cervical foraminotomy (PECF) is one of minimally invasive surgical techniques for cervical radiculopathy. Because of minimal disruption of posterior cervical structures, such as facet joint, cervical kinematics was minimally changed. However, a larger resection of facet joint is required for cervical foraminal stenosis (FS) than disc herniation (DH). The objective was to compare the cervical kinematics between patients with FS and DH after PECF. METHODS: Consecutive 52 patients (DH, 34 vs. FS, 18) who underwent PECF for single-level radiculopathy were retrospectively reviewed. Clinical parameters (neck disability index, neck pain and arm pain), and segmental, cervical and global radiological parameters were compared at postoperative 3, 6, and 12 months, and yearly thereafter. A linear mixed-effect model was used to assess interactions between groups and time. Any occurrence of significant pain during follow-up was recorded during a mean follow-up period of 45.5 months (range 24-113 months). RESULTS: Clinical parameters improved after PECF, with no significant differences between groups. Recurrent pain occurred in 6 patients and surgery (PECF, anterior discectomy and fusion) was performed in 2 patients. Pain-free survival rate was 91% for DH and 83% for FS, with no significant difference between the groups (P = 0.29). Radiological changes were not different between groups (P > 0.05). Segmental neutral and extension curvature became more lordotic. Cervical curvature became more lordotic on neutral and extension X-rays, and the range of cervical motion increased. The mismatch between T1-slope and cervical curvature decreased. Disc height did not change, but the index level showed degeneration at postoperative 2 years. CONCLUSION: Clinical and radiological outcomes after PECF were not different between DH and FS patients and kinematics were significantly improved. These findings may be informative in a shared decision-making process.

Genetic Odyssey to Ossification of the Posterior Longitudinal Ligament in the Cervical Spine: A Systematic Review.

Despite numerous studies, the pathogenesis of ossification of the posterior longitudinal ligament (OPLL) is still unclear. Previous genetic studies proposed variations in genes related to bone and collagen as a cause of OPLL. It is unclear whether the upregulations of those genes are the cause of OPLL or an intermediate result of endochondral ossification process. Causal variations may be in the inflammation-related genes supported by clinical and updated genomic studies. OPLL demonstrates features of genetic diseases but can also be induced by mechanical stress by itself. OPLL may be a combination of various diseases that share ossification as a common pathway and can be divided into genetic and idiopathic. The phenotype of OPLL can be divided into continuous (including mixed) and segmental (including localized) based on the histopathology, prognosis, and appearance. Continuous OPLL shows substantial overexpression of osteoblast-specific genes, frequent upper cervical involvement, common progression, and need for surgery, whereas segmental OPLL shows moderate-to-high expression of these genes and is often clinically silent. Genetic OPLL seems to share clinical features with the continuous type, while idiopathic OPLL shares features with the segmental type. Further genomic studies are needed to elucidate the relationship between genetic OPLL and phenotype of OPLL.

Validity of magnetic resonance imaging (MRI) in the primary spinal cord tumors in routine clinical setting.

MRI is the primary diagnostic modality for spinal cord tumors. However, its validity has never been vigorously scrutinized in daily routine clinical practice, where MRI tissue diagnosis is usually not a single one but multiple ones with several differential diagnoses. Here, we aimed to assess the validity of MRI in terms of predicting the pathology and location of the tumor in routine clinical settings. We analyzed 820 patients with primary spinal cord tumors, who have a pathological diagnosis and location in the operation record which were confirmed. We modified traditional measures for validity based upon a set of diagnoses instead of a single diagnosis. Sensitivity and specificity and positive and negative predictabilities were evaluated for the tumor location and pathology. For tumor location, 456 were intradural extramedullary; 165 were intramedullary, and 156 were extradural. The overall sensitivity and specificity were over 90.0%. However, the sensitivity became lower when the tumor resided simultaneously in two spaces such as in the intradural-and-extradural or intramedullary-and-extramedullary space (54.6% and 30.0%, respectively). Most common pathology was schwannoma (n = 416), followed by meningioma (114) and ependymoma (87). Sensitivities were 93.3%, 90.4%, and 89.7%, respectively. Specificities were 70.8%, 82.9%, and 76.0%. In rare tumors such as neurofibromas, and diffuse midline gliomas, the sensitivity was much lower (less than 30%). For common locations and pathologies, the validity of MRI is generally acceptable. However, for rare locations and pathologies, MRI diagnosis still needs some improvement.

Mechanical Failure After Total En Bloc Spondylectomy and Salvage Surgery.

OBJECTIVE: Total en bloc spondylectomy (TES) is a curative surgical method for spinal tumors. After resecting the 3 spinal columns, reconstruction is of paramount importance. We present cases of mechanical failure and suggest strategies for salvage surgery. METHODS: The medical records of 19 patients who underwent TES (9 for primary tumors and 10 for metastatic tumors) were retrospectively reviewed. Previously reported surgical techniques were used, and the surgical extent was 1 level in 16 patients and 2 levels in 3 patients. A titanium-based mesh-type interbody spacer filled with autologous and cadaveric bone was used for anterior support, and a pedicle screw/rod system was used for posterior support. Radiotherapy was performed in 11 patients (pre-TES, 5; post-TES, 6). They were followed up for 59 ± 38 months (range, 11-133 months). RESULTS: During follow-up, 8 of 9 primary tumor patients (89%) and 5 of 10 metastatic tumor patients (50%) survived (mean survival time, 124 ± 8 months vs. 51 ± 13 months; p = 0.11). Mechanical failure occurred in 3 patients (33%) with primary tumors and 2 patients (20%) with metastatic tumors (p = 0.63). The mechanical failure-free time was 94.4 ± 14 months (primary tumors, 95 ± 18 months; metastatic tumors, 68 ± 16 months; p = 0.90). Revision surgery was performed in 4 of 5 patients, and bilateral broken rods were replaced with dual cobalt-chromium alloy rods. Repeated rod fractures occurred in 1 of 4 patients 2 years later, and the third operation (with multiple cobalt-chromium alloy rods) was successful for over 6 years. CONCLUSION: Considering the difficulty of reoperation and patients' suffering, preemptive use of a multiple-rod system may be advisable.

A cost-utility analysis between decompression only and fusion surgery for elderly patients with lumbar spinal stenosis and sagittal imbalance.

Lumbar spinal stenosis (LSS) and sagittal imbalance are relatively common in elderly patients. Although the goals of surgery include both functional and radiological improvements, the criteria of correction may be too strict for elderly patients. If the main symptom of patients is not forward-stooping but neurogenic claudication or pain, lumbar decompression without adding fusion procedure may be a surgical option. We performed cost-utility analysis between lumbar decompression and lumbar fusion surgery for those patients. Elderly patients (age > 60 years) who underwent 1-2 levels lumbar fusion surgery (F-group, n = 31) or decompression surgery (D-group, n = 40) for LSS with sagittal imbalance (C7 sagittal vertical axis, C7-SVA > 40 mm) with follow-up ≥ 2 years were included. Clinical outcomes (Euro-Quality of Life-5 Dimensions, EQ-5D; Oswestry Disability Index, ODI; numerical rating score of pain on the back and leg, NRS-B and NRS-L) and radiological parameters (C7-SVA; lumbar lordosis, LL; the difference between pelvic incidence and lumbar lordosis, PI-LL; pelvic tilt, PT) were assessed. The quality-adjusted life year (QALY) and incremental cost-effective ratio (ICER) were calculated from a utility score of EQ-5D. Postoperatively, both groups attained clinical and radiological improvement in all parameters, but NRS-L was more improved in the F-group (p = 0.048). ICER of F-group over D-group was 49,833 US dollars/QALY. Cost-effective lumbar decompression may be a recommendable surgical option for certain elderly patients, despite less improvement of leg pain than with fusion surgery.

Interlaminar Endoscopic Lumbar Discectomy: A Narrative Review.

BACKGROUND: When pain caused by lumbar disc herniation (LDH) is not relieved after 4 to 6 weeks of conservative treatment, surgery is recommended. Open microdiscectomy is a standard surgical technique, but surgical endoscopy enables endoscopic lumbar surgery with clinical outcomes similar to those of standard microdiscectomy. Endoscopic lumbar discectomy is largely divided into transforaminal endoscopic lumbar discectomy (TELD) and interlaminar endoscopic lumbar discectomy (IELD). TELD was introduced about 10 years earlier than IELD and seems to be more popular than IELD. OBJECTIVE: The present article reviews the surgical technique, indications, and outcomes of IELD. Although much is still unknown, potential future perspectives are reviewed. SUMMARY: Although improved surgical techniques enable TELD to be versatile, IELD is still specifically beneficial for patients with highly migrated LDH and a high iliac crest. There is a large body of literature indicating favorable outcomes with both TELD and IELD. Currently, the selection of TELD or IELD is at the discretion of the surgeon, but the IELD surgical technique is useful for further applying endoscopic lumbar surgery for lumbar decompression or lumbar interbody fusion. The techniques can be assisted by advanced technologies such as artificial intelligence, surgical robots, and artificial reality, and a precise and systematic approach to decision-making and surgical techniques is required to combine these technologies effectively.

The Efficacy of Lumbar Hybrid Fusion for the Prevention of Adjacent Segment Disease: Fact or Artifact? A Meta-analysis.

STUDY DESIGN: A systematic literature review and meta-analysis. OBJECTIVE: The aim of this study is to compare hybrid constructs with traditional fusion-only constructs for the incidence of adjacent segment degeneration (ASDeg) and clinical outcomes in patients with degenerative lumbar diseases. SUMMARY OF BACKGROUND DATA: Spinal fusion is a standard surgery for various pathologies of the lumbar spine, which results in changes to the biomechanics of the spine, potentially leading to ASDeg. Although ASDeg can occur slowly as a natural course, early-onset ASDeg is regarded to be related to fusion surgery. MATERIALS AND METHODS: A systematic search was conducted to identify studies that match the purpose. Included studies were compared using the incidence of ASDeg, Oswestry Disability Index, Visual Analog Score, and perioperative outcomes. We calculated the Peto odds ratio and mean difference (MD) for the continuous variables, respectively. In the hybrid group, subgroup analysis was also performed among devices. RESULTS: Among 10 papers involving 767 patients, 372 patients underwent hybrid fusion and 395 patients underwent fusion-only. ASDeg occurred in 10.2% in the hybrid and 21.5% in the fusion-only group [Peto odds ratio, 0.39; 95% confidence interval (CI), 0.23-0.64]. The MD for Visual Analog Score were 0.45 (95% CI, 0.05-0.85) between 2 groups, which was statistically significant but was too small to have clinical significance. The MD for Oswestry Disability Index was 0.93 (95% CI, -1.016 to 2.872), which was not statistically different between 2 groups. The hybrid is superior for 18 minutes (95% CI, 5.78-30.72) shorter than typical surgery. CONCLUSIONS: Hybrid lumbar surgery decreased the incidence of early-onset ASDeg for about 2 years of follow-up. Among the hybrid constructs, the interspinous devices group accomplished favorable results with a lower risk. Adjacent segment disease was not as statistically significant as ASDeg, but adjacent segment disease may show a substantial difference for >2-year follow-up.

The Use Fibrin Sealant after Spinal Intradural Tumor Surgery: Is It Necessary?

OBJECTIVE: A fibrin sealant is commonly applied after closure of an incidental or intended durotomy to reduce the complications associated with the leakage of cerebrospinal fluid. Routine usage might not be essential after closure of an intended durotomy, which has clear cut-margins. We investigated the efficacy of fibrin sealants for primary intradural spinal cord tumor surgery. METHODS: A retrospective review was performed for 231 consecutive surgically treated patients with primary intradural spinal cord tumors without extradural extension. Fibrin sealants were not used for 47 patients (group I: age, 51.57±16.75 years) and were applied to 184 patients (group II: age, 48.8±14.7 years). The surgical procedures were identical except for the use of a fibrin sealant after closure of the durotomy. The primary outcome was the occurrence of complications (wound problems, hematoma collection, infection, and neurological deterioration). The covariates were age, sex, body mass index, operation time, pre-/postoperative ambulation, number of laminectomies, and type of tumor. RESULTS: Schwannoma was the most common pathology (n=134), followed by meningioma (n=35) and ependymoma (n=31). Complications occurred in 13 patients (3 in group I and 10 in group II, p=0.73). The postoperative ambulation status (p<0.01; odds ratio, 28.8; 95% confidence interval, 6.9-120.0) and operation time (p=0.04; cutoff, 229 minutes; sensitivity, 62%; specificity, 72%) were significant factors, whereas the use of a fibrin glue was not (p=0.47). CONCLUSION: The use of a fibrin sealant might not be essential to reduce complications after surgery for primary spinal intradural tumor.

White Matter Change Revealed by Diffusion Tensor Imaging in Gliomas.

BACKGROUND: Tumor-related white matter change is detected at late stages with magnetic resonance imaging (MRI), when mass effect or prominent edema is present. We analyzed if diffusion tensor imaging (DTI) white matter change earlier than conventional MRI. METHODS: Twenty-six patients with gliomas (World Health Organization grade II, 5; grade III, 12; and grade IV, 9) within 2 cm from the posterior limb of the internal capsule (IC) were studied. Fifteen normal adults were enrolled as controls. Fluid attenuation inversion recovery MRI showed a high signal change at the posterior limb of the IC (HSIC) in 9 patients with grade III or IV gliomas. We classified the gliomas as WHO grade II (gliomas II), grade III or IV without HSIC [gliomas III/IV(-)] and grade III or IV with HSIC [gliomas III/IV(+)], as an indicator of the increase in the severity of the white matter changes. Fractional anisotropy (FA) and apparent diffusion coefficients (ADC) were calculated for the pyramidal tract. Tumor progression along pyramidal tract was evaluated by follow-up MRI in 16 patients at 40±18 months. RESULTS: FA showed no significant difference between gliomas II and control (p=0.694), but was lower in gliomas III/IV(-) and gliomas III/IV(+) (p<0.001). ADCs were higher in gliomas II, gliomas III/IV(-) and gliomas III/IV(+) than control (p<0.001). Tumor progression was detected in 2/16 patients. CONCLUSION: DTI detected white matter changes that appeared to be normal in MRI. ADC changed even in low grade glioma, indicating ADC may be a better parameter for the early detection of white matter change.

Delayed diagnosis of probable radiation induced spinal cord vascular disorders.

Occasionally, unexpected neurological deficits occur after lumbar spinal surgery. We report a case of monoparesis after lumbar decompressive surgery. A 63-year-old man, who had undergone decompression of L4-5 for spinal stenosis 4 days previously in the other hospital, visted the emergency department with progressive weakness in the left leg and hypoesthesia below sensory level T7 on the right side. He had been cured of lung cancer with chemotherapy and radiation therapy 10 years previously, but detailed information of radiotherapy was not available. Whole spine magnetic resonance (MR) imaging showed fatty marrow change from T1 to T8, most likely due to previous irradiation. The T2-weighted MR image showed a high-signal T4-5 spinal cord lesion surrounded by a low signal rim, and the T1-weighted MR image showed focal high signal intensity with focal enhancement. The radiological diagnosis was vascular disorders with suspicious bleeding. Surgical removal was refused by the patient. With rehabilitation, the patient could walk independently without assistance 2 months later. Considering radiation induced change at thoracic vertebrae, vascular disorders may be induced by irradiation. If the spinal cord was previously irradiated, radiation induced vascular disorders needs to be considered.