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.

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.

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.

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.

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.

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.

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.

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.

How analgesia-sedation alters monocyte mCD14 and HLA-DR levels in patients undergoing cerebral angiography?

AIM: This study aims to evaluate how analgesia-sedation causes alterations of HLA-DR and cytokines (IL-10 and IL-6) in patients undergoing cerebral angiography for several cerebral vascular diseases. MATERIAL AND METHODS: This study includes 41 males who underwent cerebral angiography. The study sample was divided into two: Group I had 7 patients who did not receive and group II had 34 patients who received analgesia-sedation before cerebral angiography. A venous blood sample was collected before and after cerebral angiography. RESULTS: Analgesia-sedation caused significant increase CD4+ and CD19 T lymphocytes (p < 0.001) but group I showed significant increase in CD40, CD154, and MHC-II levels (p < 0.001) after cerebral angiography. CONCLUSION: We suggest that the effects of fentanyl and midazolam on the immune response are the reflection of the effects by the monocyte, mHLA-DR expression. In the future, depending on the immunological status of the patients, different anesthetic applications including the new anesthetic agents that will be able to decrease immune system suppression will be required.

Pallidal deep brain stimulation in a 5-year-old child with dystonic storm: case report.

A 5-year-old child had a medical history of epilepsy and a newly presented mental retardation with a life-threatening dystonic storm. Neuroimagings showed bilateral calcification of the pallidum. Several treatment modalities were performed, but the symptoms showed no significant improvement. The patient was operated on in order to place a deep brain stimulation (DBS) targeting bilateral globus pallidum internus (GPi). The dystonia showed a remarkable improvement after surgery, with 81% reduction of dystonia severity after 15 months. To our best knowledge, this is the youngest patient mentioned in the literature to be treated with DBS, which was also life-saving in this case.

Unilateral thalamic Vim and GPi stimulation for the treatment of Holmes' tremor caused by midbrain cavernoma: case report and review of the literature.

A 30-year-old man with brainstem cavernoma experienced hemorrhage and was operated in 2008. Six months after the operation, the patient presented with new complaints of left arm tremor namely Holmes' tremor. Neurological examination also revealed left-sided internuclear ophthalmoplegia, left-sided mild paresis, and increased deep tendon reflexes of the left upper extremity, truncal ataxia, and dysarthria. Brain magnetic resonance imaging showed a postoperative cavity and gliosis at the level of the superior and inferior colliculus in the right tegmentum and right red nucleus with extension to the substantia nigra. Fahn-Tolosa-Marin tremor rating scale (TRS) for his left upper extremity (Part A, score 6) was 11 for the proximal and the distal arm. After the failure of medical treatment, the patient underwent right globus pallidum internus and ventral intermediate thalamic nucleus deep brain stimulation. There were no side effects related to the stimulation. Final TRS months after operation was 3 for the proximal and 4 for the distal arm.

TH1 and TH2 Cytokines Production and NK Cell Level Assessment in Peripheral Blood of Patients with DDH.

In this study, our aim is; if the studies will quide us in peripheral blood, for the changes in inflammatory cytokine levels we defined before DDH tissue. Twenty-six patients were suggestive of lumbar DDH were included in this study. Control subjects included 14 autopsy cases. From each patient, disc tissues and peripheral blood samples for plasma were collected during the surgery. For the controls, disc samples and blood for plasma by intracardiac puncture were obtained during autopsy. The Flow Cytometry was used to obtain the lymphocyte CD56 (NK). The Luminex was used to obtain IL-2, IL-4, IL-10, IL-12, IFN-gamma, in both plasma and disc tissues. The results were compared between the two groups. Comparing the two groups regarding plasma demonstrated that IL-2, IL-4, IL-12, IFN-gamma were significantly higher than in patients than those of the controls. Likewise, tissue levels of IL-2, IL-4, IL-10, IL-12, TNF-alpha, CD56 were found to be significantly higher in the patients. With respect to the comparison between the plasma disc samples in the patients, plasma showed significant higher levels of IL-2, IL-12 on the other hand IL-4 was found to be significantly higher in the disc samples. Findings suggest that only tissue samples responses in occurring but not blood samples. We don't think our results in peripheral blood will guide us specifically in DDH.

The effects of analgesia-sedation on the immune system before and after cerebral digital subtraction angiography.

AIM: Cerebral digital subtraction angiography (DSA) is an invasive procedure and may cause inflammatory responses in the body. This study aims to provide cytokine and lymphocyte profile in a population of patients underwent cerebral DSA. MATERIAL AND METHODS: Forty-one male patients who admitted for cerebral DSA were included in this study. Patients were divided into two groups: Group I (n = 7) included patients who did not receive analgesia-sedation and group II (n = 34) received analgesia-sedation before procedure. For the molecules, a venous blood samples from every patient was collected before and after cerebral DSA. RESULTS: Cytokine levels in group I showed a trend to increase in the majority of the molecules after the procedure except IL-1ß. In group II, cytokines showed variable trend. When comparing the two groups regarding cytokine levels after cerebral DSA, IL-1ß, IL-10, IL-12, and IFN-γ levels increased significantly in group II. Comparing the two groups with respect to lymphocytes after cerebral DSA showed that CD56 levels were significantly higher in group II and other parameters did not show significant differences. CONCLUSION: It can be possible that delimitation of the action(s) of the cytokines affecting the secretion or activation of CD56 (natural killer) may avoid complications of inflammation after invasive procedures.

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.