The Relationship Between Inflammatory Processes and Apoptosis in Lumbar Disc Degeneration.

OBJECTIVE: Degenerative Disc Disease (DDD) is a common health problem in the population. There are recent studies focusing on relationship between DDD and immunological factors. However, there is still a lack of data on the role of apoptosis in DDD pathophysiology. Therefore, we aimed to investigate the relationship between Modic-type changes and the apoptosis in DDD. MATERIALS AND METHODS: Ninety adult male patients who presented with low back and/or radicular pain and were operated on due to lumbar disc herniation were included. Three groups were formed based on Modic type degeneration observed on magnetic resonance imaging. Specific parameters involved in the intrinsic and extrinsic pathways of apoptosis were assessed in excised disc materials using the enzyme-linked immunosorbent assay method. RESULTS: All three groups formed according to Modic degeneration types were homogenous in all variances. Cytochrome-C was significantly decreased only in the Modic type-3 group, whereas Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor-1, B-Cell Lymphoma-2 (Bcl-2) Homologous Antagonist Killer-1, Direct Inhibitor of Apoptosis-Binding Protein with Low Pi, and Bcl-2 Associated X Apoptosis Regulator levels were significantly different in both Modic type-2 and -3 groups. However, BH3 interacting domain death agonist and Bcl-2 levels were similar across all groups. CONCLUSIONS: In conclusion, this study suggests that Direct Inhibitor of Apoptosis-Binding Protein with Low Pi, cytochrome - c, Bcl-2 Associated X Apoptosis Regulator, Bcl-2 Homologous Antagonist Killer-1, and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor-1proteins play important roles in the development and progression of DDD and are correlated with Modic types. Further studies are needed to explore the potential therapeutic role of inhibiting these apoptotic proteins in DDD.

Transpedicular Corpectomy and Anterior Column Reconstruction for the Treatment of Traumatic Thoracolumbar Fractures.

AIM: To retrospectively analyze the results obtained from the posterior-only approach in non-pathological traumatic thoracolumbar body fractures with spinal cord compression. MATERIAL AND METHODS: A total of 17 patients with traumatic non-pathological thoracolumbar fractures were included in the study. Demographic details include preoperative data such as neurological status, deformity, pain scores, and radiology; intraoperative data such as blood loss, duration of surgery, and complications, and postoperative data including the neurologic status; the duration of hospital stay, pain scores, and deformity correction were analyzed. RESULTS: Among the 17 patients, 8 were in ASIA A, 9 had incomplete neurologic deficits (ASIA C - D), and none was neurologically intact (ASIA E) preoperatively. All patients had TLICS scores > 4 and were treated surgically. The mean TLICS score was 7.31. Although no worsening was detected in the neurological images of the patients during the postoperative period, neurological improvement of at least one ASIA grade was detected in 13 patients. However, it was found that the neurological functions remained the same in the 4 patients. With significant improvement, the mean preoperative VAS score was 8.2, while the mean postoperative VAS score was 3.3. In addition, satisfactory outcomes were obtained in radiological examinations, both in terms of kyphotic deformity and vertebral body collapse. CONCLUSION: Traumatic thoracolumbar fractures can be effectively fixed with the posterior-only approach and the transpedicular route. One of the most significant advantages of this procedure is that peripheral decompression, reduction, anterior column reconstruction, and instrumentation all can be performed simultaneously in the same session.

Can TRIF/TICAM-1 Dependent Pathway be Target Pathway in Lumbar Intervertebral Disc Degeneration?

AIM: To elucidate the role of the TIR-domain-containing adaptor-inducing interferon-? (TRIF) dependent pathway in intervertebral disc degeneration (IVD). MATERIAL AND METHODS: A total of adult male patients with low back pain (LBP) (+/- radicular pain) were further evaluated by magnetic resonance imaging (MRI) with surgical indication for microscopic lumbar disc herniation (LDH). Preoperatively, patients were classified according to Modic Changes (MC), nonsteroidal anti-inflammatory drugs (NSAIDs) use, and the presence of radicular pain in addition to the LBP. RESULTS: The age of the 88 patients ranged from 19 to 75 years (mean: 47.3 ± 19.6 years). Twenty eight of the patients were evaluated as MC I (31.8%), 40 as MC II (45.4%), and 20 as MC III (22.7%). The majority of patients (81.8%) had radicular LBP, while 16 patients (18.1%) had only LBP. Predominantly, 55.6% of all patients were taking NSAIDs. Levels of all adaptor molecules were highest in the MC I group and lowest in the MC III group. The levels of IRF3, TICAM1, TICAM2, NF-kB p65, TRAF6, and TLR4 were significantly increased in the MC I group compared to the MC II and MC III groups. The variations of the individual adaptor molecules showed no statistically significant difference in the use of NSAIDs and radicular LBP. CONCLUSION: As a result of the impact assessment, the current study clearly demonstrated for the first time that the TRIFdependent signalling pathway plays a crucial role in the degeneration process in human lumbar intervertebral disc specimens.

Posterior-only approach in patients with poor general condition and spinal metastatic vertebral fracture.

PURPOSE: The surgical treatment of spinal metastases is mostly palliative in nature and focuses on improving the quality of life of patients. The posterior transpedicular surgical approach provides circumferential 360° decompression, allows reconstruction and stabilisation to be achieved in a single session and can be performed using an open, mini-open or minimally invasive approach. We present and discuss the surgical techniques and outcomes for patients with single-level metastatic spinal disease and in poor general condition who underwent surgery via the posterior-only transpedicular corpectomy approach and reconstruction with expandable corpectomy cages. METHODS: Patients with a single level thoracolumbar metastatic disease (T3-L5) and a Karnofsky score of ≤70, who underwent a complete posterior transpedicular corpectomy with expandable cage reconstruction of the anterior spinal column were retrospectively reviewed. Patients' demographics, SINS, modified Tokuhashi scores as well as preoperative and postoperative ASIA scale, Karnofsky scores, VAS scores and vertebral height/Cobb angle values were analysed. RESULTS: A total of 44 patients (24 M/20 F) (mean age 53.25±21.26 years) met the inclusion criteria. The modified Tokuhashi scores were as follows: score 0-8, 5 (11.4%) patients; score 9-11, 14 (31.8%) patients; and score 12-15, 25 (56.8%) patients. There were significant improvements in the postoperative VAS scores (mean 7.7-2.9), Karnofsky scores (mean 63.3-79.6) as well as the Cobb angles (18.6-12.8°) and vertebral height. Thirtyfive patients showed improved neurological function by at least one ASIA grade, whereas 9 showed no improvement during the postoperative period. CONCLUSIONS: This technique, which has a low complication rate and a short recovery time, can help achieve satisfactory results even in patients with poor metabolic profiles and Karnofsky scores in the preoperative period. Further clinical studies with large patient groups are warranted to confirm the results of this study.

Role of the MyD88 Dependent Pathway in Degenerative Disc Disease.

AIM: To define the substantial role of the TLR4 signaling pathway in the MyD88-dependent pathway, and to evaluate the results of TLR4 activation in nucleus pulposus cells. Moreover, we aim to associate this pathway with intervertebral disc degeneration and magnetic resonance imaging (MRI) findings. Additionally, the clinical differences among patients and the effects of their drug use will be evaluated. MATERIAL AND METHODS: Eighty-eight adult male patients with lower back pain and sciatica underwent MRI studies, which showed degenerative changes. Disc materials were obtained intraoperatively from those who underwent surgery for lumbar disc herniation. These materials were kept in freezers at ?80°C without any delay. Then, the collected materials were examined using enzyme-linked immunosorbent assays. RESULTS: Modic type I degeneration had the highest values of all markers, whereas Modic type III degeneration had the lowest values. These results verified that this pathway plays an active role in MD. Moreover, contrary to the current knowledge on which Modic type inflammation is more dominant, we showed that it is the Modic type I phase. CONCLUSION: The most intense inflammatory process was observed in Modic type 1 degeneration, and the MyD88-dependent pathway was found to play a key role. While the most intense molecular increase was detected in Modic type 1 degeneration, the lowest levels were observed in Modic type III degeneration. It has been observed that the use of nonsteroidal anti-inflammatory drugs affects the inflammatory process through the MyD88 molecule.

The relationship between the ratio of interpedicular distance increase and the ratio of spinal canal compromise in thoracolumbar burst fractures.

BACKGROUND: The aim of the study was to investigate the relationship between the interpedicular distance increase ratio and the ratio of canal compromise in thoracolumbar burst fractures. METHODS: Thirty-one patients (18 male and 13 female) with an average age of 30.8 (14-57) who had been treated for thoraco-lumbar burst fractures in the Department of Orthopaedics and Traumatology were included in the study. The initial anteroposterior radiographs of the patients were used to calculate the increase ratio of interpedicular distance (both from medial-to-medial and from center-to-center). The area measurements from the computerized tomography or magnetic resonans images were used to calculate the canal compromise. The relationship between the increase ratio of interpedicular distance and the ratio of canal compromise was investigated by correlation and linear regression analysis. RESULTS: There was a 'very good' correlation between the from medial-to-medial and from center-to-center measurements of interpedicular distance (Pearson correlation coefficient: 0.89, p<0.001). The correlation between the ratio of canal compromise and from medial-to-medial and from center-to-center measurements of interpedicular distance was 'good' with Pearson correlation coef-ficients of 0.60 and 0.63, respectively (p<0.001). No statistically significant relationships were found between the fracture levels, types, neurologic status of the patients, and the increase ratio of interpedicular distance or the ratio of canal compromise. CONCLUSION: Depending on the correlation coefficients which were obtained in this study: To predict the canal compromise from the ratio of interpedicular distance increase is not a reliable method for all of the patients.

Treatment of homocystinuria-related dystonia with deep brain stimulation: a case report.

A 23-year-old woman with the medical history of homocystinuria that had been diagnosed at the age of 14 has been non-responsive to treatment. The patient presented with the symptoms of dysphonia, dysarthria and severe dystonia of the neck and left extremities. Blood and urine biochemistry revealed high levels of homocystine. Brain magnetic resonance imaging was normal with no detectable pathologies. Medical treatment strategies were used and repeated injections of botulinum toxin A were administered, but the symptoms showed no significant improvement. The patient was then operated, and deep brain stimulators targeting the bilateral globus pallidus internus were implanted. After the activation of the electrodes, dystonia symptoms showed a remarkable improvement. Good outcome was documented during the follow-up period of 7 months. To our best knowledge, this is the first reported case of homocystinuria-related dystonia symptoms that were successfully treated with deep brain stimulation.

Comparison of two surgical techniques in Chiari Malformation Type 1 Patients: Duraplasty alone vs duraplasty with arachnoid dissection.

OBJECT: Optimal surgical technique to restore the cerebrospinal fluid flow through the foramen magnum remains to be debated in Chiari malformation type 1 (CM-1) patients. METHOD: This study included 46 patients with CM-1 who underwent surgical treatment by one of two methods: posterior fossa bone decompression (BD) with arachnoid preserving duraplasty (Group 1) and BD with duraplasty and arachnoid dissection (Group 2). Complaints of the patient population and neurological findings were assessed with Neck Disability Index (NDI) and Europe Quality of Life 5 Dimensions (EQ-5D) in pre- and postoperative periods. RESULTS: NDI and EQ-5D scores improved in overall patient population and in each individual surgical group. Both groups showed a significant decrease in size of syringomyelia cavity. Complications resulting in recurrent treatments and re-operations occurred in 15% of patients (n = 7); six of them were from Group 2. CONCLUSION: CM-1 patients benefit significantly from surgical treatment. Duraplasty should be included to surgical technique. Avoiding arachnoid dissection may lead to better results regarding complication rates.

Catabolic cytokine expressions in patients with degenerative disc disease.

AIM: Lumbar degenerative disc disease (DDD) is a common disease of advanced age characterized by progressive changes in the intervertebral disc and associated structures. There have been great efforts for years to explain its pathophysiological mechanism(s). This study aims to provide cytokine profile and in addition to the lymphocytes in a population of patients with lumbar DDD. MATERIAL AND METHODS: Twenty-six patients whose clinical and radiological features were suggestive of lumbar DDD that underwent surgery and 14 autopsy cases as control were included. Patient disc samples were obtained during surgery whilst disc materials were collected during autopsy procedures from the controls. Major cytokines and lymphocytes were studied by using the flow cytometry method. RESULTS: Significantly higher levels in disc samples in relation to IL-1ß, IL-2, IL-4, IL-10, IL-12, TNF-α, CD8, CD56, CD19, and CD40 were found in the patients compared to the controls. Positive correlations were shown between CD3/CD4, CD25/CD3, CD25/CD4, CD19/CD4 but negative correlations were shown between CD19/CD3 and CD25/CD19 in both groups. CONCLUSION: The findings suggest that both local inflammatory responses occur in lumbar DDD. Using specific cytokines either by local or systemic application may reverse the degenerative process.

Comparative Analysis of NF-κB in the MyD88-Mediated Pathway After Implantation of Titanium Alloy and Stainless Steel and the Role of Regulatory T Cells.

OBJECTIVE: Development of immunologically smart implants, integrated to biological systems, is a key aim to minimize the inflammatory response of the host to biomaterial implants. METHODS: The aim of this study is to investigate the influence of titanium alloy and stainless steel implants on immunological responses in rats by comparative analysis of nuclear factor kappa B (NF-κB) profiles in the activation of inflammatory signaling pathways and the role of CD4+CD25+Foxp3+. RESULTS: Both Ti alloy and stainless steel alloy group implantation affect Toll-like receptors-4 pathways and CD4+CD25+ regulatory T cells in different ways. CONCLUSIONS: Results show that NF-κB/p65 and NF-κB1/p50 possess potential as a therapeutic target in the prevention of adverse reactions to metal, especially for controlling inflammation after the implantation.

Bilateral C1-C2 claw for atlantoaxial instability.

OBJECTIVE: Atlantoaxial stability can be achieved by laminar hook systems via posterior approach. This technique is much more safer than using screws. We presented our experience with the C1-C2 claw procedure. METHODS AND MATERIAL: Seven patients with atlantoaxial instability were operated by using C1 and C2 hooks, rods and transverse connector at Neurosurgery Clinic of Istanbul University Cerrahpasa Medical Faculty between the years 2005 and 2008. RESULTS: Satisfactory stabilization was achieved in all patients. Operative complication or instrumentation failure was not observed. CONCLUSIONS: C1-C2 claw is a safe technique and adequate stabilization is achieved with the use of a transverse connector.

Intraoperative Neuromonitoring in Surgery of Cauda Equina and Conus Medullaris Tumors.

AIM: To demonstrate the value of special intraoperative neuromonitoring techniques for cauda equina and conus medullaris tumors (CECMT) by describing standard methods used at our center. MATERIAL AND METHODS: Neurophysiological records were retrospectively reviewed for 16 patients (eight females and eight males; age range: 27â€"60 years) who underwent surgery for CECMT at our department between 2016 and 2018. RESULTS: Motor and/or sensorial deficits were preoperatively identified in 10 patients; no patients had bladder or sexual dysfunction. Motor evoked potential (MEP) loss occurred in seven patients with full or partial recovery. No changes were seen in pudendal somatosensory evoked potential (SEP) or bulbocavernosus reflex (BCR), and morphological deterioration and amplitude loss of tibial SEPs were present in four patients. Postoperatively, no new neurological deficits and/or bladder and sexual dysfunction were present. CONCLUSION: Pudendal SEP and BCR are useful tests for monitoring CECMT surgeries. BCR is an easily obtainable modality for preserving sacral functions and recommended as a primary monitoring modality in conjunction with traditional neurophysiological techniques during CECMT surgery.

Posturographic examination of body balance in patients with Chiari type I malformation and correlation with the presence of syringomyelia and degree of cerebellar ectopia.

OBJECTIVES: We aimed to evaluate balance using the Tetrax Interactive Balance System (TIBS) in patients with Chiari type I malformation (CM-I) and to assess their fall risk with other clinical parameters. PATIENTS AND METHODS: This cross-sectional, prospective study was conducted at physical medicine and rehabilitation outpatient clinics and neurosurgery department of a university hospital between December 2013 and December 2014. The study included a total of 36 patients (31 females, 5 males; mean age 40.6±10.0 years; range, 18 to 60 years) with CM-I. Dynamic balance was assessed using the Berg Balance Scale (BBS), and posturographic examinations were performed using the TIBS. RESULTS: The mean Fall Risk Index (FI) value was 42.4±29.8 and the mean BBS score was 55.5±1.5. The most common complaints were neck pain (94.4%), headache (88.9%), paresthesia (86.1%), fatigue (83.3%), and vertigo (80.6%). The mean tonsillar herniation below the foramen magnum was 8.7±3.8 (mm). Of the patients, 15 (42.85%) had syringomyelia. The degree of tonsillar ectopia was statistically significantly lower in patients with syringomyelia (p<0.05). The BBS scores were near identical among the patients with or without syringomyelia, although the FI values were lower in the patients with syringomyelia. Comparing cerebellar ectopia ≤9 mm versus >10 mm, the FI values were slightly higher in the patients with ectopia >10 mm, although there was no statistically significant difference in the FI or BBS values. CONCLUSION: Our study results suggest that CM-I can decrease the body balance stability and, thus, increase the fall risk. Evaluation of balance in patients with CM using TIBS static posturography is a simple and effective technique.

Spinal Vascular Malformations: Treatment and Outcome.

BACKGROUND: Vascular malformations of the spinal cord are a rare and complex clinical entity and can lead to severe morbidity with progressive spinal cord symptoms if not treated properly. In early stages, the disease is characterized by slowly progressive, nonspecific symptoms, such as gait disturbance, paresthesia, diffuse sensory symptoms, and radicular pain; in the late stages, bowel and bladder incontinence, erectile dysfunction, and urinary retention may develop. In recent decades, understanding and treatment of spinal vascular malformations have improved with the evolution of diagnostic tools and treatment modalities; however, it is still difficult to manage these cases because of the complexity of the pathology. The aims of this study were to present the long-term outcomes of our patients and to discuss the optimal management strategies. METHODS: We reviewed the records of 78 patients with spinal vascular malformations and performed a retrospective, single-center case series evaluating initial occlusion, recanalization, retreatment, and neurologic status of patients with dural arteriovenous fistulas, perimedullary arteriovenous fistulas, arteriovenous malformations, and extradural arteriovenous fistulas who had undergone embolization and/or surgery. RESULTS: No mortality was observed. Complete obliteration was achieved in 76 patients (97.4%). CONCLUSIONS: Both endovascular and surgical treatment of spinal vascular malformations resulted in significant long-term recovery from myelopathic symptoms and improvement in quality of life for most patients.

Intracranial hypotension following scoliosis surgery: dural penetration of a thoracic pedicle screw.

The authors report on a 14 years old female with intracranial hypotension who had a history of spinal instrumentation surgery for scoliosis 3 months prior to her admission. She had been diagnosed with migraine in a neurology clinic and was under medical therapy when presented. During the investigation process, a right thoracic pedicle screw, which was penetrating and transversing the dura mater at the T3-T4 level was identified. The diagnosis and management of such a case is discussed. Knowledge of this entity is of extreme importance to spine surgeons, in order to prevent delayed diagnosis and possible complications.

Acute tetraplegia following laryngotracheal reconstruction surgery.

BACKGROUND: Paraplegia following thoracic spinal surgery or abdominal operations is usually attributed to spinal cord ischemia due to interruption of the segmental spinal vascular supply. Alternatively, the etiology of spinal cord ischemia following cervical surgery is less clear. CASE DESCRIPTION: A 14-year-old male became acutely tetraplegic with a C4 sensory level and sphincteric dysfunction 12 h following surgery for tracheal stenosis due to prior intubation. Signs included loss of pain and temperature below the level of C4 with preservation of deep sensations (position and vibration) and mute plantar responses. The cervical magnetic resonance imaging revealed diffuse intramedullary cord swelling between C2-C7 and hyperintense signal changes in the anterior and posterior columns of the cord on T2-weighted images. Various etiologies for this finding included a cervical hyperextension or hyperflexion injury vs. anterior spinal artery syndrome. CONCLUSIONS: Postoperative treatment of spinal cord ischemia attributed to cervical and thoracoabdominal surgery is largely ineffective in reversing major neurological deficits. Therefore, it is critical to prevent ischemia during these procedures by the avoidance of coagulopathies, anemia, hypotension, and hyperflexion/hyperextension maneuvers.

Concomitant fracture of bilateral occipital condyle and inferior clivus: what is the mechanism of injury?

With the routine use of multi-slice high resolution computed tomography, increasing number of occipital condyle fractures have been reported in the last decade. The authors report a very rare case of bilateral occipital condyle fracture complicated by the fracture of the inferior clivus and discuss the possible mechanisms of injury.

Intrathecal baclofen toxicity and deep coma in minutes.

BACKGROUND/OBJECTIVE: In recent years, intrathecal baclofen (ITB) treatment in patients with refractory spasticity has been accepted as an effective therapy. However, this treatment modality may cause life-threatening complications. This report describes the clinical presentation, unfamiliar dilemmas, and treatment of a patient with ITB toxicity and raises awareness of problems that may arise. METHODS: A 33-year-old man with refractory spasticity due to diffuse white matter injury was admitted for ITB treatment. The patient had respiratory difficulty followed by a generalized seizure and developed coma minutes after the drug administration. The patient was transferred into an intensive care unit immediately and managed accordingly. RESULTS: After proper management, the patient was followed and continued to receive ITB treatment. CONCLUSIONS: ITB therapy is a very effective method of rehabilitation and medication in patients with refractory spasticity, but physicians must be aware of the serious complications that may develop just minutes after the drug is administered. Although safe, baclofen pumps are nevertheless mechanical devices that may malfunction. Therefore, physicians should be mindful of the possibility of life-threatening complications that may develop and lead to a patient's death if proper treatment is not performed.

Finite element method based stress analysis of zone I and zone II sacral fractures.

BACKGROUND: Sacral bone fractures after direct traumas such as gunshot wounds and blunt sacral traumas are rarely, whereas those occurring after indirect traumas with vertical shear mechanisms ( car accidents or falls) are more frequently seen. METHODS: A cadaver sacrum was modelled 3-dimensionally using finite element software. Left sacroiliac joint was modeled to simulate a 75- kg man falling on one leg from a height of 5 meters. An impact load of 10 kN was transferred to the sacrum via intervertebral disc surface and two facets. Von Mises equivalent stress distribution was estimated. RESULTS: Von Mises stress distribution was calculated for sacral ala (430 MPa), S1 pedicle (225 MPa), and S1 lamina (35 MPa). Stress values were 200 Mpa, 130 Mpa, 105 Mpa, and 55 MPa on ventrolateral, dorsomedial, ventromedial and dorsolateral sides of S1 foramen respectively. Vertical shear injury caused stress distribution to concentrate at sacral ala and S1 pedicle (zone I). Local stress distribution around S1 foramen is concentrated ventrolaterally CONCLUSION: High incidence of zone I sacral fractures and low incidence of neurological deficits could be explained by concentration of stress at sacral ala. Zone II fractures might be due to by transfer of triggered stresses from sacral ala and S1 pedicle to ventrolateral side of S1 foramen.