The renin-angiotensin system has an important role in the pathogenesis of stroke. We investigated whether two missense single nucleotide polymorphisms (SNPs; rs4762, Thr207Met, T207M; and rs699, Met268Thr, M268T) of angiotensinogen (AGT; serpin peptidase inhibitor, clade A, member 8) are associated with the development and clinical phenotypes of ischemic stroke (IS) and intracerebral hemorrhage (ICH). We analyzed 197 stroke patients (120 IS and 77 ICH) and 301 control subjects. The patients were classified into subgroups in accordance to the scores of the National Institutes of Health Stroke Survey (NIHSS, <6 and ≥6) and Modified Barthel Index (MBI, <60 and ≥60). Multiple logistic regression models were used to analyze the genotype and allele distributions of each SNP. One of the missense SNPs, rs4762 (T207M) was associated with the development of ICH (P=0.038 in log-additive model and P=0.021 in allele distributions). The T allele frequency of T207M was higher in the ICH group (16.2%) compared with the control group (9.6%). The TC haplotype frequency differed significantly between the ICH and control groups (P=0.014). With regard to clinical features, T207M correlated with the NIHSS scores of the ICH patients (P=0.039 in codominant1, P=0.015 in dominant, P=0.011 in overdominant and P=0.039 in log-additive models). However, the two missense SNPs, rs4762 and rs699, were not associated with IS and its clinical features, including NIHSS and MBI scores. These data suggest that a missense SNP (rs4762, T207M) of the AGT gene may be associated with the development of ICH and contribute to the neurological functional levels of ICH patients.
angiotensinogen; haplotype; intracerebral hemorrhage; ischemic stroke; single nucleotide polymorphism
We present the rare case of solitary xanthogranuloma in the upper cervical column mimicking a Brown-Sequard syndrome. A 29-year-old man complained with right hemiparesis and left hypoesthesia after a car accident. Computed tomography and magnetic resonance images revealed a lobulated homogenously well-enhancing mass in between posterior arch of the atlas (C1) and spinous process of the axis (C2) resulting in a marked spinal canal narrowing with cortical erosions. The patient was managed by complete resection of the tumor with partial laminectomy with lower half of C1 posterior arch and upper half of C2 spinous process. The authors advise complete removal of the xanthogranuloma and consideration as a differential diagnosis of lesions among upper cervical lesions.
Juvenile xanthogranuloma; Xanthogranuloma; Cervical vertebrae; Brown-Sequard syndrome
The extracellular matrix (ECM) and cell adhesion molecules play crucial roles in angiogenesis, apoptosis, thrombosis, and inflammation, and also contribute to the pathogenesis of stroke. Integrin, alpha 6 (ITGA6) is a member of ECM adhesion receptors. We investigated whether two single nucleotide polymorphisms (SNPs) (rs11895564, Ala380Thr; rs2293649, Asp694Asp) of ITGA6 were associated with the development and clinical phenotypes of intracerebral hemorrhage (ICH) and ischemic stroke (IS).
We enrolled 199 stroke (78 ICH and 121 IS) and 291 control subjects. Stroke patients were divided into subgroups according to the scores of the National Institutes of Health Stroke Survey (NIHSS, <6 and ≥6) and Modified Barthel Index (MBI, <60 and ≥60). SNPStats, SNPAnalyzer, and Helixtree programs were used to calculate odds ratios, 95% confidence intervals, and p values. Multiple logistic regression models were used to analyze genetic data.
A missense SNP rs11895564 was associated with the development of ICH (p=0.026 in codominant2, p=0.013 in recessive, p=0.02 in log-additive models; p=0.041 in allele distributions). The A allele frequency of rs11895564 was higher in the ICH group (13.5%) than in the control group (8.1%). In the clinical phenotypes, rs11895564 and rs2293649 showed significant associations in the MBI scores of IS (p=0.014 in codominant1 model; p=0.02 in allele distributions) and NIHSS scores of ICH (p=0.017 in codominant2, p=0.035 in recessive, p=0.035 in log-additive models), respectively.
These results suggest that ITGA6 may be associated with the development and clinical phenotypes of stroke in Korean population.
Intracerebral hemorrhage; Ischemic stroke; Polymorphism; Integrin, alpha 6
Chronic non-specific low back pain is the most common medical problem for which patients seek complementary and alternative medical treatment, including bee venom acupuncture. However, the effectiveness and safety of such treatments have not been fully established by randomized clinical trials. The aim of this study is to determine whether bee venom acupuncture is effective for improving pain intensity, functional status and quality of life of patients with chronic non-specific low back pain.
This study is a randomized, double-blinded, sham-controlled clinical trial with two parallel arms. Fifty-four patients between 18 and 65 years of age with non-radicular chronic low back pain experiencing low back pain lasting for at least the previous three months and ≥4 points on a 10-cm visual analog scale for bothersomeness at the time of screening will be included in the study. Participants will be randomly allocated into the real or sham bee venom acupuncture groups and treated by the same protocol to minimize non-specific and placebo effects. Patients, assessors, acupuncturists and researchers who prepare the real or sham bee venom acupuncture experiments will be blinded to group allocation. All procedures, including the bee venom acupuncture increment protocol administered into predefined acupoints, are designed by a process of consensus with experts and previous researchers according to the Standards for Reporting Interventions in Clinical Trials of Acupuncture. Bothersomeness measured using a visual analogue scale will be the primary outcome. Back pain-related dysfunction, pain, quality of life, depressive symptoms and adverse experiences will be measured using the visual analogue scale for pain intensity, the Oswestry Disability Index, the EuroQol 5-Dimension, and the Beck’s Depression Inventory. These measures will be recorded at baseline and 1, 2, 3, 4, 8 and 12 weeks.
The results from this study will provide clinical evidence on the efficacy and safety of bee venom acupuncture in patients with chronic non-specific low back pain.
This study is registered with the United States National Institutes of Health Clinical Trials Registry: NCT01491321
Bee venom acupuncture; Chronic low back pain
To present the accuracy and safety of cervical pedicle screw insertion using the technique with direct exposure of the pedicle by laminoforaminotomy.
We retrospectively reviewed 12 consecutive patients. A total of 104 subaxial cervical pedicle screws in 12 patients had been inserted. We also assessed the clinical and radiological outcomes and analyzed the direction and grade of pedicle perforation (grade 0: no perforation, 1: <25%, 2: 20% to 50%, 3: >50% of screw diameter) on the postoperative vascular-enhanced computed tomography scans. Grade 2 and 3 were considered as incorrect position.
The correct position was found in 95 screws (91.3%); grade 0-75 screws, grade 1-20 screws and the incorrect position in 9 screws (8.7%); grade 2-6 screws, grade 3-3 screws. There was no neurovascular complication related with cervical pedicle screw insertion.
This technique (technique with direct exposure of the pedicle by laminoforaminotomy) could be considered relatively safe and easy method to insert cervical pedicle screw.
Cervical pedicle screw; Laminoforaminotomy; Pedicle perforation
To document lumbar lordosis (LL) of the spine and its change during surgeries with the different height but the same angle setting of the anterior cage. Additionally, we attempted to determine if sufficient LL is achieved at different cage heights and to quantify the change in LL during multi-level anterior lumbar interbody fusion (ALIF).
The medical records and radiographs of 42 patients who underwent more than 2 level ALIFs between 2008 and 2009 were retrospectively reviewed. We evaluated 3 parameters seen on lateral whole spine radiographs : LL, pelvic incidence (PI), and sagittal vertical axis (SVA). The mean follow-up time was 28.1 months and the final follow-up radiographs of all patients were reviewed at least 2 years after surgery. Statistical analysis was performed using the paired t-tests.
Lumbar lordosis had changed up to 30 degrees immediately and 2 years after surgery (preoperative mean LL, SVA : 22.45 degrees, 112.31 mm; immediate postoperative mean LL, SVA : 54.45 degrees, 37.36 mm; final follow-up mean LL, SVA : 49.56 degrees, 26.95 mm). Our goal of LL is to obtain as much PI as possible, preoperative mean PI value was 55.38±3.35. The pre-operative and two year post-surgery follow-up mean of the Japanese Orthopedic Association score were 9.2±0.6 and 13.2±0.6 (favorable outcome rate : 95%), respectively. In addition, we were able to obtain good clinical outcomes and sagittal balance with a subsidence rate of 22.7%.
We were able to achieve sufficient LL, such that it was similar to the PI, utilizing multi-level ALIF with the use of a tall cage with the same angle setting of the cage. We have found out that achieving sufficient lumbar lordosis and sagittal balance require an anterior lumbar cage with high angle and height.
ALIF; Anterior interbody fusion; Multilevel ALIF; Pelvic incidence; Anterior lumbar cage; Sagittal balance
The aim of this study was to determine whether anterior column support is required in Smith-Petersen osteotomy procedure with correction angles of more than 10°, while examining the subsequent healing patterns in relation to the disrupted area.
An analysis was done on 26 segments of 19 patients who showed a correction angle of more than 10° in the anterior opening after SPO. There were 17 male and two female patients with a mean age of 40 years (24–56 years). The mean follow-up period was 6.5 years (2–9.1 years). The patients were classified according to the site of the anterior opening, as the disc level, the lower end-plate of the upper body (upper body), or the upper end-plate of the lower body (lower body). The healing patterns of anterior opening and the radiological correction angles were evaluated relative to the opening site.
In all cases, bony fusion was confirmed at a mean period of 5.6 months (3–6.7 months) after surgery and the anterior opening gap was healed in 18 segments (69.2%). For patients that developed an opening in the upper body, all of the gaps were healed. The gaps in the lower body opening group were healed in 85.7% of the cases, and for the opening at the disc level, the gaps were healed only in 12.5% of the cases. The least amount of correction was obtained when anterior opening occurred in disc level.
In our study of subjects presenting with anterior opening angles from 10° to 32°, we obtained successful fusion without the need for additional anterior interbody fusion. Improved gap healing and increased correction angles were obtained when the opening was present in the upper or lower body endplates compared to those at the disc space level.
Ankylosing spondylitis; Kyphotic deformity; Smith-Petersen osteotomy
The rat middle cerebral artery thread-occlusion model has been widely used to investigate the pathophysiological mechanisms of stroke and to develop therapeutic treatment. This study was conducted to analyze energy metabolism, apoptotic signal pathways, and genetic changes in the hippocampus of the ischemic rat brain.
Focal transient cerebral ischemia was induced by obstructing the middle cerebral artery for two hours. After 24 hours, the induction of ischemia was confirmed by the measurement of infarct size using 2,3,5-triphenyltetrazolium chloride staining. A cDNA microarray assay was performed after isolating the hippocampus, and was used to examine changes in genetic expression patterns.
According to the cDNA microarray analysis, a total of 1,882 and 2,237 genes showed more than a 2-fold increase and more than a 2-fold decrease, respectively. When the genes were classified according to signal pathways, genes related with oxidative phosphorylation were found most frequently. There are several apoptotic genes that are known to be expressed during ischemic brain damage, including Akt2 and Tnfrsf1a. In this study, the expression of these genes was observed to increase by more than 2-fold. As energy metabolism related genes grew, ischemic brain damage was affected, and the expression of important genes related to apoptosis was increased/decreased.
Our analysis revealed a significant change in the expression of energy metabolism related genes (Atp6v0d1, Atp5g2, etc.) in the hippocampus of the ischemic rat brain. Based on this data, we feel these genes have the potential to be target genes used for the development of therapeutic agents for ischemic stroke.
Apoptosis; Energy metabolism; Focal cerebral ischemia; Gene expression; Hippocampus; Oxidative phosphorylation
Ossification of the posterior longitudinal ligament (OPLL) has a strong genetic component. Specific gene polymorphisms may be associated with OPLL in several genes which regulate calcification in chondrocytes, change of extracellular collagen matrix and secretions of many growth factors and cytokines controlling bone morphogenesis. Toll-like receptor 5 (TLR5) may play a role in the pathogenesis of OPLL by intermediate nuclear factor-kappa B (NF-κB). The current study focused on coding single nucleotide polymorphisms (SNPs) of TLR5 for a case-control study investigating the relationship between TLR5 and OPLL in a Korean population.
A total of 166 patients with OPLL and 231 controls were recruited for a case-control association study investigating the relationship between SNPs of TLR5 gene and OPLL. Four SNPs were genotyped by direct sequencing (rs5744168, rs5744169, rs2072493, and rs5744174). SNP data were analyzed using the SNPStats, SNPAnalyzer, Haploview, and Helixtree programs. Multiple logistic regression analysis with adjustment for age and gender was performed to calculate an odds ratio (OR).
None of SNPs were associated with OPLL in three alternative models (codominant, dominant, and recessive models; p > 0.05). A strong linkage disequilibrium block, including all 4 SNPs, was constructed using the Gabriel method. No haplotype was significantly associated with OPLL in three alternative models.
These results suggest that Toll-like receptor 5 gene may not be associated with ossification of the posterior longitudinal ligament risk in Korean population.
OPLL; TLR5 gene; Polymorphisms; Genetic association study
To evaluate the clinical and radiological outcomes of lumbar interbody fusion and its correlation with various factors (e.g., age, comorbidities, fusion level, bone quality) in patients over and under 65 years of age who underwent lumbar fusion surgery for degenerative lumbar disease.
One-hundred-thirty-three patients with lumbar degenerative disease underwent lumbar fusion surgery between June 2006 and June 2007 and were followed for more than one year. Forty-eight (36.1%) were older than 65 years of age (group A) and 85 (63.9%) were under 65 years of age (group B). Diagnosis, comorbidities, length of hospital stay, and perioperative complications were recorded. The analysis of clinical outcomes was based on the visual analogue scale (VAS). Radiological results were evaluated using plain radiographs. Clinical outcomes, radiological outcomes, length of hospital stay, and complication rates were analyzed in relation to lumbar fusion level, the number of comorbidities, bone mineral density (BMD), and age.
The mean age of the patients was 61.2 years (range, 33-86 years) and the mean BMD was -2.2 (range, -4.8 to -2.8). The mean length of hospital stay was 15.0 days (range, 5-60 days) and the mean follow-up was 23.0 months (range, 18-30 months). Eighty-five (64.0%) patients had more than one preoperative comorbidities. Perioperative complications occurred in 27 of 133 patients (20.3%). The incidence of overall complication was 22.9% in group A, and 18.8% in group B but there was no statistical difference between the two groups. The mean VAS scores for the back and leg were significantly decreased in both groups (p < 0.05), and bony fusion was achieved in 125 of 133 patients (94.0%). There was no significant difference in bony union rates between groups A and B (91.7% in group A vs. 95.3% in group B, p = 0.398). In group A, perioperative complications were more common with the increase in fusion level (p = 0.027). Perioperative complications in both groups A (p = 0.035) and B (p = 0.044) increased with an increasing number of comorbidities.
Elderly patients with comorbidities are at a high risk for complications and adverse outcomes after lumbar spine surgery. In our study, clinical outcomes, fusion rates, and perioperative complication rates in older patients were comparable with those in younger populations. The number of comorbidities and the extent of fusion level were significant factors in predicting the occurrence of postoperative complications. However, proper perioperative general supportive care with a thorough fusion strategy during the operation could improve the overall postoperative outcomes in lumbar fusion surgery for elderly patients.
Elderly patients; Lumbar interbody fusion; Comorbidities; Complications
The management of lower cervical fractures in patients with ankylosing spondylitis (AS) differs from normal cervical fractures. Patients with AS are highly susceptible to extensive neurologic injuries and spinal deformities after cervical fractures from even minor traumatic forces. These injuries are uniquely complex, require careful imaging assessment, and aggressive surgical management to optimize spinal stability and functional outcomes.
Ankylosing spondylitis; Lower cervical spine fracture
Acupuncture appears to be a clinically effective treatment for acute and chronic pain. A considerable amount of research has been conducted to evaluate the role that acupuncture plays in pain suppression; however, few studies have been conducted to evaluate the side effects of the acupuncture procedure. This case report describes a suspected postdural puncture headache following acupuncture for lower back pain. Considering the high opening pressure, cerebrospinal fluid leakage, and the patient's history of acupuncture in the lower back area, our diagnosis was iatrogenic postdural puncture headache. Full relief of the headache was achieved after administration of an epidural blood patch.
Acupuncture; Iatrogenic complication; Postdural puncture headache
Nontraumatic intracranial subarachnoid hemorrhage (SAH) attributable to the thoracolumbar dural arteriovenous fistulas (DAVFs) has been extremely rare. A 41-year-old male patient was admitted with severe acute headache, neck stiffness, and pronounced low-back pain radiating to both legs. The T2-weighted MR imaging showed irregular signal void and enlarged, varix like pouch formation with spinal cord compression at the T11-12 level. The angiogram revealed a DAVF.
We report a DAVF case with SAH that revealed an extensive infarction from C5 to the conus medullaris after undergoing operative treatment.
Dural arteriovenous fistula; Subarachnoid hemorrhage; Spinal cord infarction
The presence of distant metastases from differentiated thyroid carcinoma decreases the 10-year survival rates of patients by 50%. This is a report of a 61-year-old female with follicular thyroid carcinoma who presented initially with low back pain. 2-deoxy-2-[18F] fluoro-D-glucose whole-body positron emission tomography/computed tomography (PET/CT) demonstrated a hypointensity lesion in the left thyroid gland with malignant uptake in L1 vertebra and magnetic resonance images revealed paravertebral and epidural extension of mass in L1 vertebra. After thyroidectomy, histopathological study showed a follicular carcinoma. We performed L1 total en bloc spondylectomy with expandable cage for long-term local control. The technical details of total en bloc spondylectomy in follicular carcinoma are described herein.
Thyroid carcinoma; Total en bloc spondylectomy; Metastasis
To evaluate the surgical outcomes of ventral interbody grafting and anterior or posterior spinal instrumentation for the treatment of advanced spondylodiscitis in patients who had failed medical management.
A total of 28 patients were evaluated for associated medical illness, detected pathogen, level of involved spine, and perioperative complications. Radiological evaluation including the rate of bony union, segmental Cobb angle, graft- and instrumentation-related complications, and clinical outcomes by mean Frankel scale and VAS score were performed.
There are 14 pyogenic spondylodiscitis, 6 postoperative spondylodiscitis, and 8 tuberculous spondylodiscitis. There were 21 males and 7 females. Mean age was 51 years, with a range from 18 to 77. Mean follow-up period was 10.9 months. Associated medical illnesses were 6 diabetes, 3 pulmonary tuberculosis, and 4 chronic liver diseases. Staphylococcus was the most common pathogen isolated (25%), and Mycobacterium tuberculosis was found in 18% of the patients. Operative approaches, either anterior or posterior spinal instrumentation, were done simultaneously or delayed after anterior aggressive debridement, neural decompression, and structural interbody bone grafting. All patients with neurological deficits improved after operation, except only one who died from aggravation as military tuberculosis. Mean Frankel scale was changed from 3.78±0.78 preoperatively to 4.78±0.35 at final follow up and mean VAS score was improved from 7.43±0.54 to 2.07±1.12. Solid bone fusion was obtained in all patients except only one patient who died. There was no need for prolongation of duration of antibiotics and no evidence of secondary infection owing to spinal instrumentations.
According to these results, debridement and anterior column reconstruction with ventral interbody grafting and instrumentation is effective and safe in patients who had failed medical management and neurological deficits in advanced spondylodiscitis.
Advanced spondylodiscitis; Ventral interbody grafting; Spinal instrumentation
Although a significant correction of local kyphosis has been reported previously, only a few studies have investigated whether this correction leads to an improved overall sagittal alignment. The study objective was to determine whether an improvement in the local kyphotic angle improves the overall sagittal alignment. We examined and compared the effects of thoracic and lumbar level kyphoplasty procedures on local versus overall sagittal alignment of the spine.
Thirty-eight patients with osteoporotic vertebral compression fractures who showed poor response to conventional, palliative medical therapy underwent single-level kyphoplasty. The pertinent clinical data of these patients, from June 2006 to November 2006, were reviewed retrospectively. We measured preoperative and postoperative vertebral body heights, which were classified as anterior, middle, or posterior fractured vertebral body heights. Furthermore, the local and overall sagittal angles after polymethylmethacrylate deposition were measured.
More height was gained at the thoracic level, and the middle vertebral height regained the most. A significant local kyphosis correction was observed at the fractured level, and the correction at larger spanning segments decreased with the distance from the fractured level.
The inflatable balloon kyphoplasty procedure was the most effective in regaining the height of the thoracic fractured vertebra in the middle vertebral body. The kyphosis correction by kyphoplasty was mainly achieved in the fractured vertebral body. Sagittal angular correction decreased with an increase in the distance from the fractured vertebra. No significant improvement was observed in the overall sagittal alignment after kyphoplasty. Further studies in a larger population are required to clarify this issue.
Kyphoplasty; Vertebral compression fracture; Sagittal alignment