Current Knowledge and Future Therapeutic Prospects in Symptomatic Intervertebral Disc Degeneration

Intervertebral disc (IVD) degeneration is the main source of intractable lower back pain, and symptomatic IVD degeneration could be due to different degeneration mechanisms. In this article, we describe the molecular basis of symptomatic IVD degenerative disc diseases (DDDs), emphasizing the role of degeneration, inflammation, angiogenesis, and extracellular matrix (ECM) regulation during this process. In symptomatic DDD, pro-inflammatory mediators modulate catabolic reactions, resulting in changes in ECM homeostasis and, finally, neural/vascular ingrowth-related chronic intractable discogenic pain. In ECM homeostasis, anabolic protein-regulating genes show reduced expression and changes in ECM production, while matrix metalloproteinase gene expression increases and results in aggressive ECM degradation. The resultant loss of normal IVD viscoelasticity and a concomitant change in ECM composition are key mechanisms in DDDs. During inflammation, a macrophage-related cascade is represented by the secretion of high levels of pro-inflammatory cytokines, which induce inflammation. Aberrant angiogenesis is considered a key initiative pathologic step in symptomatic DDD. In reflection of angiogenesis, vascular endothelial growth factor expression is regulated by hypoxia-inducible factor-1 in the hypoxic conditions of IVDs. Furthermore, IVD cells undergoing degeneration potentially enhance neovascularization by secreting large amounts of angiogenic cytokines, which penetrate the IVD from the outer annulus fibrosus, extending deep into the outer part of the nucleus pulposus. Based on current knowledge, a multi-disciplinary approach is needed in all aspects of spinal research, starting from basic research to clinical applications, as this will provide information regarding treatments for DDDs and discogenic pain.

A Prospective, Multi-Center, Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of the Synthetic Bone Graft Material DBM Gel with rhBMP-2 versus DBM Gel Used during the TLIF Procedure in Patients with Lumbar Disc Disease

Objective@#: This study is to evaluate the efficacy and safety of demineralized bone matrix (DBM) gel versus DBM gel with recombinant human bone morphogenetic protein-2 (rhBMP-2) used in transforaminal lumbar interbody fusion (TLIF). @*Methods@#: This study was designed as a prospective, multi-center, double-blind method, randomized study. All randomized subjects underwent TLIF with DBM gel with rhBMP-2 group (40 patients) as an experimental group or DBM gel group (36 patients) as a control group. Post-operative observations were performed at 12, 24, and 48 weeks. The spinal fusion rate on computed tomography scans and X-rays films, Visual analog scale pain scores, Oswestry disability index and SF-36 quality of life (QOL) scores were used for the efficacy evaluation. The incidence rate of adverse device effects (ADEs) and serious adverse device effects (SADEs) were used for safety evaluation. @*Results@#: The spinal fusion rate at 12 weeks for the DBM gel with rhBMP-2 group was higher with 73.68% compared to 58.82% for the DBM gel group. The 24 and 48 weeks were 72.22% and 82.86% for the DBM gel with rhBMP-2 group and 78.79% and 78.13%, respectively, for the DBM gel group. However, there were no significant differences between two groups in the spinal fusion rate at 12, 24, and 48 weeks post-treatment (p=0.1817, p=0.5272, p=0.6247). There was no significant difference between the two groups in the incidence rate of ADEs (p=0.3836). For ADEs in the experimental group, ‘Pyrexia’ (5.00%) was the most common ADE, followed by ‘Hypesthesia’, ‘Paresthesia’, ‘Transient peripheral paralysis’, ‘Spondylitis’ and ‘Insomnia’ (2.50%, respectively). ADEs reported in control group included ‘Pyrexia’, ‘Chest discomfort’, ‘Pain’, ‘Osteoarthritis’, ‘Nephropathy toxic’, ‘Neurogenic bladder’, ‘Liver function analyses’ and ‘Urticaria’ (2.86%, respectively). There was no significant difference between the two groups in the incidence rate of SADEs (p=0.6594). For SADE in the experimental group, ‘‘Pyrexia’ and ‘Spondylitis’ were 2.50%. SADE reported in the control group included 'Chest discomfort’, ‘Osteoarthritis’ and ‘Neurogenic bladder’. All SADEs described above were resolved after medical treatment. @*Conclusion@#: This study demonstrated that the spinal fusion rates of DBM gel group and DBM gel with rhBMP-2 group were not significantly different. But, this study provides knowledge regarding the earlier postoperative effect of rhBMP-2 containing DBM gel and also supports the idea that the longer term follow-up results are essential to confirm the safety and effectiveness.

Hepatopulmonary Syndrome with Finger Clubbing / 대한내과학회지

Hepatopulmonary syndrome is a rare lung complication of liver cirrhosis, caused by pulmonary microvascular vasodilation that induces abnormal arterial oxygenation. Typical findings on physical examination are finger clubbing and cyanosis. Dyspnea is a common symptom and is worse in the upright position. Contrast echocardiography is a useful diagnostic test. Currently, the only effective treatment is liver transplantation. We report the case of a woman with cirrhosis who has hepatopulmonary syndrome with finger clubbing, confirmed by contrast echocardiography. The patient is waiting for a liver transplant.

A Prospective, Multi-Center, Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of the Synthetic Bone Graft Material DBM Gel with rhBMP-2 versus DBM Gel Used during the TLIF Procedure in Patients with Lumbar Disc Disease

Objective@#: This study is to evaluate the efficacy and safety of demineralized bone matrix (DBM) gel versus DBM gel with recombinant human bone morphogenetic protein-2 (rhBMP-2) used in transforaminal lumbar interbody fusion (TLIF). @*Methods@#: This study was designed as a prospective, multi-center, double-blind method, randomized study. All randomized subjects underwent TLIF with DBM gel with rhBMP-2 group (40 patients) as an experimental group or DBM gel group (36 patients) as a control group. Post-operative observations were performed at 12, 24, and 48 weeks. The spinal fusion rate on computed tomography scans and X-rays films, Visual analog scale pain scores, Oswestry disability index and SF-36 quality of life (QOL) scores were used for the efficacy evaluation. The incidence rate of adverse device effects (ADEs) and serious adverse device effects (SADEs) were used for safety evaluation. @*Results@#: The spinal fusion rate at 12 weeks for the DBM gel with rhBMP-2 group was higher with 73.68% compared to 58.82% for the DBM gel group. The 24 and 48 weeks were 72.22% and 82.86% for the DBM gel with rhBMP-2 group and 78.79% and 78.13%, respectively, for the DBM gel group. However, there were no significant differences between two groups in the spinal fusion rate at 12, 24, and 48 weeks post-treatment (p=0.1817, p=0.5272, p=0.6247). There was no significant difference between the two groups in the incidence rate of ADEs (p=0.3836). For ADEs in the experimental group, ‘Pyrexia’ (5.00%) was the most common ADE, followed by ‘Hypesthesia’, ‘Paresthesia’, ‘Transient peripheral paralysis’, ‘Spondylitis’ and ‘Insomnia’ (2.50%, respectively). ADEs reported in control group included ‘Pyrexia’, ‘Chest discomfort’, ‘Pain’, ‘Osteoarthritis’, ‘Nephropathy toxic’, ‘Neurogenic bladder’, ‘Liver function analyses’ and ‘Urticaria’ (2.86%, respectively). There was no significant difference between the two groups in the incidence rate of SADEs (p=0.6594). For SADE in the experimental group, ‘‘Pyrexia’ and ‘Spondylitis’ were 2.50%. SADE reported in the control group included 'Chest discomfort’, ‘Osteoarthritis’ and ‘Neurogenic bladder’. All SADEs described above were resolved after medical treatment. @*Conclusion@#: This study demonstrated that the spinal fusion rates of DBM gel group and DBM gel with rhBMP-2 group were not significantly different. But, this study provides knowledge regarding the earlier postoperative effect of rhBMP-2 containing DBM gel and also supports the idea that the longer term follow-up results are essential to confirm the safety and effectiveness.

A New Classification for Cervical Ossification of the Posterior Longitudinal Ligament Based on the Coexistence of Segmental Disc Degeneration

Objective@#: Classification systems for cervical ossification of the posterior longitudinal ligament (OPLL) have traditionally focused on the morphological characteristics of ossification. Although the classification describes many clinical features associated with the shape of the ossification, including the concept of spondylosis seems necessary because of the similarity in age distribution. @*Methods@#: Patients diagnosed with OPLL who presented with increase signal intensity (ISI) on magnetic resonance imaging were surgically treated in our department. The patients were divided into two groups (pure versus degenerative) according to the presence of disc degeneration. @*Results@#: Of 141 patients enrolled in this study, more than half (61%) were classified into the degenerative group. The pure group showed a profound male predominance, early presentation of myelopathy, and a different predilection for ISI compared to the degenerative group. The mean canal compromise ratio (CC) of the ISI was 47% in the degenerative group versus 61% in the pure group (p<0.0000). On the contrary, the global and segment motions were significantly larger in the degenerative group (p<0.0000 and p=0.003, respectively). The canal diameters and global angles did not differ between groups. @*Conclusion@#: Classifying cervical OPLL based on the presence of combined disc degeneration is beneficial for understanding the disorder’s behavior. CC appears to be the main factor in the development of myelopathy in the pure group, whereas additional dynamic factors appear to affect its development in the degenerative group.

Hepatopulmonary Syndrome with Finger Clubbing / 대한내과학회지

Hepatopulmonary syndrome is a rare lung complication of liver cirrhosis, caused by pulmonary microvascular vasodilation that induces abnormal arterial oxygenation. Typical findings on physical examination are finger clubbing and cyanosis. Dyspnea is a common symptom and is worse in the upright position. Contrast echocardiography is a useful diagnostic test. Currently, the only effective treatment is liver transplantation. We report the case of a woman with cirrhosis who has hepatopulmonary syndrome with finger clubbing, confirmed by contrast echocardiography. The patient is waiting for a liver transplant.

Coronavirus Disease (COVID-19) Outbreak and Its Impact on Spinal Daily Practice : Preliminary Report from a Single (Regional) University Hospital in Republic of Korea

Objective@#: Since the first discovery of the 2019 novel coronavirus (COVID-19), rapid and wide spread of the disease has been reported and the World Health Organization announced that a ‘pandemic’ has started. Up to date there is little known regarding the impact of this outbreak on spinal specialists’ daily clinical practice. We intended to evaluate how COVID-19 has affected the number of spinal disease patients we meet and operate in daily practice. @*Methods@#: The de-identified data regarding number of patients visiting the spine clinic at a tertiary referral hospital and a secondary level hospital from January, February and March of 2017 to 2020 were retrospectively reviewed. The number of out-patient department (OPD) visits, number of emergency room (ER) visits as well as number of surgeries performed during the reviewed period were collected and analyzed, comparing 2020 to the previous 3 years. @*Results@#: The number of daily OPD visits showed a steady decrease starting from January, and presented a statistically significant decrease by early March 2020, compared to the previous 3 years. During the same period, decrease in number of daily ER visits was statistically significant as well. The number of elective surgeries or number of surgeries for patients admitted via ER during COVID-19 outbreak remained similar to that of 2017–2019 suggesting, despite the decrease of patients visiting the hospital for spinal diseases, those whom required surgery still visited the hospital. The results were consistant among other hospital level. @*Conclusion@#: The outbreak of COVID-19 affected our daily practice as OPD and ER visits reduced but did not affect the number of surgeries. We believe that this report will be informative to spinal specialists worldwide fighting the COVID-19 pandemic.

A Rare Case of Lumbar Traumatic Intradiscal Hematoma Followed by Repeatative Occupation Related Minor Trauma

A case of surgically treated intervertebral disc extrusion with intraoperatively confirmed intradiscal hematoma in a 30-year-old physical trainer is presented. Preoperative magnetic resonance imaging revealed downward migrating disc herniation, without definite suggestive findings of intradiscal hematoma. Intervertebral disc herniation with concomitant intradiscal hematoma is extremely rare, but could occur in patients who have excessive axial stress to the spine occupationally. In our case, the patient was an occupational physical trainer who had repetitive minor trauma to the lumbar spine. Although the patient did not have any clear history of major trauma to the spine, the intraoperative findings revealed intradiscal hematoma, which is very rare. The presence of intradiscal hematoma is to be suspected even when preoperative imaging studies shows indefinite findings of hematoma, considering the change in signal intensity of hematoma by time.

Non-Operatively Treated Thoracolumbar Burst Fracture with Posterior Ligamentous Complex Injury: Case Report and Consideration on the Limitation of Thoracolumbar Injury Classification and Severity (TLICS) Score

Fractures at the thoracolumbar region are commonly followed after major traumatic injuries, and up to 20% of these fractures are known to be burst fractures. Making surgical decisions for these patients are of great interest however there is no golden standard so far. Since the introduction of Thoracolumbar Injury Classification and Severity (TLICS) score in 2007, it has been widely used as a referential guideline for making surgical decisions in thoracolumbar fractures. However, there is still limitations in this system. In this clinical case report, we introduce a L1 burst fracture after motor vehicle injury, who was successfully treated conservatively even while she was graded as a TLICS 5 injury. A case report is presented as well as discussion on the limitations of this grading system.

Prevalence of Neuropathic Pain and Patient-Reported Outcomes in Korean Adults with Chronic Low Back Pain Resulting from Neuropathic Low Back Pain

STUDY DESIGN: A noninterventional, multicenter, cross-sectional study. PURPOSE: We investigated the prevalence of neuropathic pain (NP) and patient-reported outcomes (PROs) of the quality of life (QoL) and functional disability in Korean adults with chronic low back pain (CLBP). OVERVIEW OF LITERATURE: Among patients with CLBP, 20%–55% had NP. METHODS: Patients older than 20 years with CLBP lasting for longer than three months, with a visual analog scale (VAS) pain score higher than four, and with pain medications being used for at least four weeks before enrollment were recruited from 27 general hospitals between December 2014 and May 2015. Medical chart reviews were performed to collect demographic/clinical features and diagnosis of NP (douleur neuropathique 4, DN4). The QoL (EuroQoL 5-dimension, EQ-5D; EQ-VAS) and functional disability (Quebec Back Pain Disability Scale, QBPDS) were determined through patient surveys. Multiple linear regression analyses were performed to compare PROs between the NP (DN4≥4) and non-NP (DN4 < 4) groups. RESULTS: A total of 1,200 patients (females: 65.7%; mean age: 63.4±13.0 years) were enrolled. The mean scores of EQ-5D, EQ-VAS, and QBPDS were 0.5±0.3, 55.7±19.4, and 40.4±21.1, respectively. Among all patients, 492 (41.0%; 95% confidence interval, 38.2%–43.8%) suffered from NP. The prevalence of NP was higher in male patients (46.8%; p < 0.01), in patients who had pain based on radiological and neurological findings (59.0%; p < 0.01), and in patients who had severe pain (49.0%; p < 0.01). There were significant mean differences in EQ-5D (NP group vs. non-NP group: 0.4±0.3 vs. 0.5±0.3; p < 0.01) and QBPDS (NP group vs. non-NP group: 45.8±21.2 vs. 36.3±20.2; p < 0.01) scores. In the multiple linear regression, patients with NP showed lower EQ-5D (β=−0.1; p < 0.01) and higher QBPDS (β=7.0; p < 0.01) scores than those without NP. CONCLUSIONS: NP was highly prevalent in Korean patients with CLBP. Patients with CLBP having NP had a lower QoL and more severe dysfunction than those without NP. To enhance the QoL and functional status of patients with CLBP, this study highlights the importance of appropriately diagnosing and treating NP.

The Korean Spinal Neurosurgery Society ; Are We Reimbursed Properly for Spinal Neurosurgical Practices under the Korean Resource Based Relative Value Scale Service?

OBJECTIVES: The Korean Resource Based Relative Value Scale (K-RBRVS) was introduced in 2001 as an alternative of the previous medical fee schedule. Unfortunately, most neurosurgeons are unfamiliar with the details of the K-RBRVS and how it affects the reimbursement rates for the surgical procedures we perform. We summarize the K-RBRVS in brief, and discuss on how the relative value (RV) of the spinal neurosurgical procedures have changed since the introduction in 2001. METHODS: We analyzed the change of spinal procedure RVs since 2001, and compared it with the change of values in the brain neurosurgical procedures. RVs of 88 neurospinal procedures on the list of K-RBRVS were analyzed, while 24 procedures added during annual revisions were excluded. RESULTS: During the past 15 years, RVs for spinal procedures have increased 62.8%, which is not so different with the cumulative increase of consumer prices during this time period or the increase rate of 92.3% for brain surgeries. When comparing the change of RVs in more complex procedures between spinal and brain neurosurgery, the increase rate was 125.3% and 133%, respectively. CONCLUSION: More effort of the society of spinal surgeons seems to be needed to get adequate reimbursement, as there have been some discrimination compared to brain surgeons in the increase of RVs. And considering the relative underestimation of spinal neurosurgeons’ labor, more objective measures of neurospinal surgeons’ work and productivity should be developed for impartial reimbursement.

Risk Factors for Delayed Hinge Fracture after Plate-Augmented Cervical Open-Door Laminoplasty

OBJECTIVE: Delayed hinge fracture (HF) that develops after cervical open door laminoplasty can be a source of postoperative complications such as axial pain. However, risk factors related to this complication remain unclear. We performed a retrospective clinical series to determine risk factors for delayed HF following plate-only open-door cervical laminoplasty. METHODS: Patients who underwent plate-only open-door laminoplasty and had available postoperative computed tomography (CT) scans (80 patients with 270 laminae) were enrolled. Hinge status, hinge gutter location, open location, hinge width, number of screws used, operation level, and open angle were observed in the CT to determine radiographic outcome. Demographic data were collected as well. Radiographic and clinical parameters were analyzed using univariate and multivariate logistic regression analysis to determine the risk factors for HF. RESULTS: Univariate logistic regression analysis results indicated poor initial hinge status, medially placed hinge gutter, double screw fixation on the elevated lamina, upper surgical level, and wide open angle as predictors for HF (p<0.05). Initial hinge status seemed to be the most powerful risk factor for HF (p=0.000) and thus was collinear with other variables. Therefore, multivariate logistic regression analysis was performed excluding initial hinge status, and the results indicated that medially placed hinge gutter, double screw fixation on the elevated lamina, and upper surgical level were risk factors for HF after adjustment for other confounding factors. CONCLUSION: To prevent HF and to draw a successful postoperative outcome after cervical laminoplasty, surgical and clinical precautions should be considered.

The Relationship between Neck Pain and Cervical Alignment in Young Female Nursing Staff

OBJECTIVE: Degenerative changes in the cervical spine are commonly accompanied by cervical kyphosis which can cause neck pain. This study examined the relationship between neck pain and cervical alignment. METHODS: A total of 323 female nursing staff from our hospital were enrolled. Sagittal radiographs of the cervical spine, Body Mass Index (BMI), Visual Analogue Scale (VAS) measures of neck and arm pain, Neck Disability Index (NDI) and the Short Form (36) Health Survey (SF-36 scores) were obtained and reviewed retrospectively. Global lordosis (GL) of the cervical spine was measured on radiograph images. Correlations between GL and questionnaire scores were investigated using the following three methods : 1) correlation between GL and questionnaire scores among the entire sample; 2) subgroup analysis of patients with "kyphosis (KYP) : GL scores0" on questionnaire measures; and 3) subgroup analysis of patients with pain vs. those without pain, on GL and questionnaire measures. RESULTS: There was no significant correlation between GL and any questionnaire measure. There was a significant difference between the mean GLs of the KYP and LOR groups, but there were no group differences in BMI, age or any questionnaire measures. There was no difference between the pain (n=92) and pain-free (n=231) groups in age, BMI or GL, but there were differences in neck, and arm pain, and physical function and NDI scores. CONCLUSIONS: Our data suggest that kyphotic deformity was not associated with neck pain.

Non-Dural-Based Spinal Meningioma : The First Case Report of a Fibrous Subtype and a Review of the Literature

Spinal meningiomas typically adhere to the dura matter. Non-dural based spinal meningiomas are rare and most are clear cell meningiomas. We report here the first case of a fibrous meningioma with non-dural attachment. The patient was a 49-year-old female, who complained of numbness in the legs and a gait disturbance. Magnetic resonance imaging revealed a 1.7x1.4-cm mass in the C7-T1 intra-dural extramedullary space, showing peripheral gadolinium enhancement without a "dural tail sign". A complete microsurgical resection was performed. The mass was covered with a white membrane but was not adhered to the dura, and its appearance was consistent with a neurilemmoma. The histopathological diagnosis was fibrous-type meningioma. The recovery of the patient was uneventful. No surgical complications and no recurrence of the tumor had occurred at the 6-month follow-up.

Matrix Degradative Enzymes and Their Inhibitors during Annular Inflammation: Initial Step of Symptomatic Intervertebral Disc Degeneration

OBJECTIVE: Symptomatic disc degeneration develops from inflammatory reactions in the annulus fibrosus (AF). Although inflammatory mediators during annular inflammation have been studied, the roles of matrix metalloproteinases (MMPs) and their inhibitors have not been fully elucidated. In this study, we evaluated the production of MMPs and tissue inhibitors of metalloproteinase (TIMPs) during annular inflammation using an in vitro co-culture system. We also examined the effect of notochordal cells on annular inflammation. METHODS: Human AF (hAF) pellet was co-cultured for 48 hours with phorbol myristate acetate-stimulated macrophage-like THP-1 cells. hAF pellet and conditioned media (CM) from co-cultured cells were assayed for MMPs, TIMPs, and insulin-like growth factor (IGF)-1 levels using real-time reverse-transcriptase polymerase chain reaction and enzyem-linked immunosorbent assay. To evaluate whether notochordal cells affected MMPs or TIMPs production on annular inflammation, hAF co-cultured with notochordal cells from adult New Zealand White rabbits, were assayed. RESULTS: MMP-1, -3, -9; and TIMP-1 levels were significantly increased in CM of hAF co-cultured with macrophage-like cells compared with hAF alone, whereas TIMP-2 and IGF-1 levels were significantly decreased (p<0.05). After macrophage exposure, hAF produced significantly more MMP-1 and -3 and less TIMP-1 and -2. Interleukin-1beta stimulation enhanced MMP-1 and -3 levels, and significantly diminished TIMP-2 levels. Co-culturing with rabbit notochordal cells did not significantly influence MMPs and TIMPs production or COL1A2 gene expression. CONCLUSION: Our results indicate that macrophage-like cells evoke annular degeneration through the regulation of major degradative enzymes and their inhibitors, produced by hAF, suggesting that the selective regulation of these enzymes provides future targets for symptomatic disc degeneration therapy.

Clinical Efficacy of Acute Monitoring Cortical Activity Using Subdural Strip Electrode after Decompressive Craniectomy / 대한신경손상학회지

OBJECTIVE: Decompressive craniectomy is widely used in cases of uncontrolled intracranial hypertension, including traumatic brain injury or acute stroke. Physiological monitorings, such as intracranial pressure or electroenecephalography (EEG) are critical for patients in the acute phase. We retrospectively reviewed our experience of continuous electrocorticography (ECoG) monitoring by subdural strip electrode in patients who performed decompressive craniectomy and assessed its clinical efficacy. METHODS: Patients who underwent decompressive craniectomy because of severe intracranial hypertension were included. 4 Channel strip electrodes were inserted on the frontal cortex before closure. 24-hour continuous monitoring of ECoG was done to identify abnormal electrical activity. The level of consciousness was assessed according to Glasgow Coma Scale (GCS). In patients with malignant intracranial hypertension, barbiturate coma therapy was considered. RESULTS: Fifteen patients (9 men and 6 women) were included and the mean age was 55.7 years (from 17 to 80). The initial mean GCS score was 7.9 (from 3 to 14). In six out of fifteen patients, abnormal spike activities were identified, and one of these six patients was diagnosed as nonconvulsive status epilepticus (NCSE). Cortical spreading depression (CSD) was suspected in five. Three patients underwent barbiturate coma therapy and ECoG monitoring of these patients showed typical burst suppression pattern, which was used for indicator of therapeutic level. The mean duration of strip electrode and ECoG monitoring was 3.5 days, and there was no complication. CONCLUSION: Continuous ECoG monitoring using subdural strip electrode was useful to detect abnormal brain activity in the acute period after decompressive craniectomy.

Nonconvulsive Seizures of Traumatic Brain Injury Patients / 대한신경손상학회지

OBJECTIVE: Seizures are common consequence of traumatic brain injury and have been reported in clinical series as an incidence of 15% to 22%. Among them, nonconvulsive seizures (NCS) are often unrecognized during the early period of neurosurgical hospitalization because their clinical presentations can be misunderstood as consequent symptoms of clinical course, and the diagnosis can be confirmed only by the electroencephalographic (EEG) recording. METHODS: We retrospectively reviewed our clinical database of traumatic brain injury (TBI) patients admitted between March 2008 and September 2012. Twenty one patients with suspicious symptoms of NCS, such as decrease of consciousness, aphasia or irritability, were included. Routine wake and sleep EEG or bedside continuous EEG monitoring were done in all patients. RESULTS: Ten out of twenty-one patients showed abnormal activities on EEG. Ictal discharges were documented on four patients. Based on clinical symptoms and EEG findings, these four patients were diagnosed as NCS. Two out of four NCS patients showed EEG findings of nonconvulsive status epilepticus (NCSE). Another six patients with abnormal EEG activities were considered as 'suspicious NCS' because only interictal activities were recorded on EEG but increasing dose or adding on antiepileptics relieved their symptoms. All NCS/NCSE were successfully controlled by appropriate antiepileptic therapy. CONCLUSION: Our result showed that NCS was diagnosed in about 20% of patients with suspicious symptoms. There's a possibility that actual NCS might have happened more. Because untreated NCS/NCSE might cause worse clinical outcome, careful observation and urgent EEG recordings should be considered in a patient with suspicious NCS symptoms.

Unusual Fatal Infections after Anterior Cervical Spine Surgeries

We report two cases of cervical spinal epidural abscess (SEA), which are related to anterior cervical surgeries. The first case reveals a late postoperative infection without any predisposing factor. The second case reveals combined complication of infection and instrument failure (artificial disc). Both two cases manifested ascending infections that are unusual courses of anterior cervical infections. The abscess extended upwards and, finally, caused life threatening bacterial meningitis. We suggest aggressive surgical interventions with anti-bacterial therapies in such cases.

Radiological Significance of Ligamentum Flavum Hypertrophy in the Occurrence of Redundant Nerve Roots of Central Lumbar Spinal Stenosis

OBJECTIVE: There were previous reports of redundant nerve roots (RNRs) focused on their clinical significance and pathogenesis. In this study, we investigated the significant radiologic findings that correlate with RNRs occurrence. These relations would provide an advanced clue for clinical significance and pathogenesis of RNRs. METHODS: Retrospective research was performed with data from 126 patients who underwent surgery for central lumbar spinal stenosis (LSS). Finally, 106 patients with common denominators (inter-observer accuracy : 84%) were included on this study. We divided the patients into two groups by MRI, patients with RNRs and those with no RNRs (NRNRs). Comparative analyses were performed with clinical and radiologic parameters. RESULTS: RNRs were found in 45 patients (42%) with central LSS. There were no statistically significant differences between the two groups in severity of symptoms. On the other hand, we found statistically significant differences in duration of symptom and number of level included (p<0.05). In the maximal stenotic level, ligamentum flavum (LF) thickness, LF cross-sectional area (CSA), dural sac CSA, and segmental angulation are significantly different in RNRs group compared to NRNRs group (p<0.05). CONCLUSION: RNRs patients showed clinically longer duration of symptoms and multiple levels included. We also confirmed that wide segmental angulation and LF hypertrophy play a major role of the development of RNRs in central LSS. Together, our results suggest that wide motion in long period contribute to LF hypertrophy, and it might be the key factor of RNRs formation in central LSS.

Notochordal Cells Influence Gene Expression of Inflammatory Mediators of Annulus Fibrosus Cells in Proinflammatory Cytokines Stimulation

OBJECTIVE: Notochordal cells in the intervertebral disc interact with nucleus pulposus (NP) cells and support the maintenance of disc homeostasis by regulation of matrix production. However, the influence of notochordal cells has not been evaluated in the annulus fibrosus (AF), which is the primary pain generator in the disc. We hypothesized that the notochordal cell has the capacity to modulate inflammatory mediators secreted by AF cells secondary to stimulation. METHODS: Notochordal and AF cells were isolated from adult New Zealand white rabbits. AF pellets were cultured with notochordal cell clusters or in notochordal cell-conditioned media (NCCM) for 24 or 48 hours with proinflammatory cytokines at varying concentrations. Gene expression in AF pellets were assayed for nitric oxide synthase (iNOS), cyclo-oxygenase (COX)-2, and interleukin (IL)-6 by real time reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: AF pellet in NCCM significantly decreased the iNOS and COX-2 messenger ribonucleic acid (mRNA) levels compared to AF pellets alone and AF pellets with notochordal cells (p < 0.05). AF pellet resulted in dose-dependent iNOS and COX-2 expression in response to IL-1beta, stimulation, demonstrating that 1 ng/ml for 24 hours yielded a maximal response. AF pellet in NCCM significantly decreased the expression of iNOS and COX-2 in response to 1ng/ml IL-1beta, stimulation at 24 hours (p < 0.05). There was no difference in IL-6 expression compared to AF pellets alone or AF pellets with notochordal cell clusters. CONCLUSION: We conclude that soluble factors from notochordal cells mitigate the gene expression of inflammatory mediators in stimulated AF, as expected after annular injury, suggesting that notochordal cells could serve as a novel therapeutic approach in symptomatic disc development.