Basar Atalay

MicroRNA expression profiling reveals the potential function of microRNA-31 in chordomas

Chordomas are rare bone tumors arising from remnants of the notochord. Molecular studies to determine the pathways involved in their pathogenesis and develop better treatments are limited. Alterations in microRNAs (miRNAs) play important roles in cancer. miRNAs are small RNA sequences that affect transcriptional and post-transcriptional regulation of gene expression in most eukaryotic organisms. Studies show that miRNA dysregulation is important for tumor initiation and progression. We compared the expression profile of miRNAs in chordomas to that of healthy nucleus pulposus samples to gain insight into the molecular pathogenesis of chordomas. Results of functional studies on one of the altered miRNAs, miR-31, are presented. The comparison between the miRNA profile of chordoma samples and the profile of normal nucleus pulposus samples suggests dysregulation of 53 miRNAs. Thirty miRNAs were upregulated in our tumor samples, while 23 were downregulated. Notably, hsa-miR-140-3p and hsa-miR-148a were upregulated in most chordomas relative to levels in nucleus pulposus cells. Two other miRNAs, hsa-miR-31 and hsa-miR-222, were downregulated in chordomas compared with the control group. Quantification with real-time polymerase chain reaction confirmed up or downregulation of these miRNAs among all samples. Functional analyses showed that hsa-miR-31 has an apoptotic effect on chordoma cells and downregulates the expression of c-MET and radixin. miRNA profiling showed that hsa-miR-31, hsa-miR-222, hsa-miR-140-3p and hsa-miR-148a are differentially expressed in chordomas compared with healthy nucleus pulposus. Our profiling may be the first step toward delineating the differential regulation of cancer-related genes in chordomas, helping to reveal the mechanisms of initiation and progression.

Efficacy of placing a thin layer of gelatin sponge over the subdural space during dural closure in preventing meningo-cerebral adhesion.

OBJECTIVE One significant drawback during a cranial reoperation is the presence of meningocerebral adhesions. The appearance of connective tissue bridges between the inner surface of the dura and the pia-arachnoid is mostly related to dural closure and the condition in which the surgical field was left in the previous surgery. This study was done to determine the benefit of placing a thin-layer gelatin sponge of polypeptides subdurally to prevent meningocerebral adhesions. METHODS From September 2005 through May 2012, 902 craniotomies were performed for various lesions by the senior author (U.T.). Beginning in February 2009, we began placing a gelatin sponge under the dural flap to isolate the dural healing process from the cortical surface. To compare the degree of meningocerebral adhesions statistically, reoperation cases between February 2009 and May 2012 were divided into 2 groups as group G (gelatin) and group C (Control) in which the dural closure was made with and without subdural application of the gelatin sponge, respectively. RESULTS In all patients of group G (n = 15), a neomembrane was found when the dura was opened. This layer was easily dissected and showed no or minimal attachment to the underlying cerebral cortex. However, in group C (n = 14), meningocerebral adhesions in various degrees were detected. Adhesion scores were significantly greater in group C than in group G (P < 0.001). CONCLUSION This study proves that, during the dural closure, placing a thin layer of gelatin sponge in the subdural space is a safe and effective method for preventing meningocerebral adhesions.

The potential function of microRNA in chordomas

Little is known about the molecular biology of chordomas, which are rare, chemoresistant tumors with no well-established treatment. miRNAs regulate gene networks and pathways. We aimed to evaluate the effects of dysregulated miRNA in chordomas would help reveal the underlying mechanisms of chordoma initiation and progression. In this study, miR-31, anti-miR-140-3p, anti-miR148a, and miR-222 were transiently transfected to chordoma cell lines and an MTS assay, apoptosis assay, and cell-cycle analysis were conducted to evaluate the effects. The mRNA level of predicted and confirmed targets of each miRNA, as well as the EMT and MET markers of U-CH1 and MUG-Chor1, were assessed with real-time polymerase chain reaction. Transient transfection of miRNA mimics was achieved, as each mimic increased or decreased the level of its corresponding miRNA. miR-31 decreased cell viability in MUG-Chor1 and U-CH2 after 72h, which is consistent with previous findings for U-CH1. Both miR-31 and anti-miR-148a induced apoptosis in all three cell lines. Although each miRNA had a similar pattern, miR-31 had the most effective S-phase arrest in all three cell lines. RDX, MET, DNMT1, DNMT3B, TRPS1, BIRC5, and KIT were found to be targeted by the selected miRNAs. The level of miR-222 in chordoma cell lines U-CH1 and MUG-Chor1 correlated positively with EMT markers and negatively with MET markers. This study uncovered the potential of miR-31, miR-140-3p, miR-148a, and miR-222-3p to be key molecules in the cell viability, cell cycle, and apoptosis in chordomas, as well as initiation, differentiation, and progression.

Vertebral augmentation by kyphoplasty and vertebroplasty: 8 years experience outcomes and complications.

Background and Context: Minimally invasive percutaneous vertebral augmentation techniques; vertebroplasty, and kyphoplasty have been treatment choices for vertebral compression fractures (VCFs). The purpose of this study is to evaluate the outcomes of the patients who underwent vertebroplasty or kyphoplasty regarding complications, correction of vertebral body height, kyphosis angle and pain relief assessment using visual analog score (VAS) for pain. Materials and Methods: A retrospective review of the hospital records for 100 consecutive patients treated with kyphoplasty or vertebroplasty in our department database. Patients with osteoporotic compression fractures, traumatic compressions, and osteolytic vertebral lesions, including metastases, hemangiomas, and multiple myeloma, were included in the study. Preoperative and postoperative VAS pain scores, percentages of vertebral compression and kyphotic angles were measured and compared as well as demographic characteristics and postoperative complications. Mobilization and length of stay (LOS) were recorded. Results: One hundred patients were treated by 110 procedures. 64 patients were operated on due to osteoporosis (72 procedures). Twelve patients were operated on because of metastasis (13 procedures), 8 patients were operated on because of multiple myeloma (9 procedures). Five patients had two surgeries, 1 patient had 3 surgeries, and 1 patient had 5 surgeries. The mean preoperative VAS was 74.05 ± 9.8. In total, 175 levels were treated, 46 levels by kyphoplasty and 129 by vertebroplasty. The mean postoperative VAS was 20.94 ± 11.8. Most of the patients were mobilized in the same day they of surgery. Mean LOS was 1.83 days. Six patients had nonsymptomatic leakage of polymethlymethacrylate, and patient had epidural hematoma, which was operated on performing hemi-laminectomy. Conclusions: Percutaneous vertebroplasty and balloon kyphoplasty are both effective and safe minimally invasive procedures for the stabilization of VCFs. However, complications should be kept in mind during decision making.

Volumetric Muscle Measurements Indicate Significant Muscle Degeneration in Single-Level Disc Herniation Patients

BACKGROUND There is a strong relationship between lower back pain and paraspinal muscle atrophy. In this study, we aimed to investigate the prevalence of lumbar paravertebral muscle atrophy in patients with and without single-level disc herniation. METHODS The 110 retrospectively analyzed patients in this study were divided into 2 groups. Group A included 55 patients with radiologically confirmed single-level disc herniation with back pain and radiculopathy. Group B included 55 patients with back pain without radiologic lumbar disc herniation. The paravertebral muscle cross-sectional areas were measured in both groups by 2 independent observers. RESULTS In total, 68 women and 42 men were examined. Their mean age was 40.85 years old. The mean ages of groups A and B were 42.49 and 39.22 years, respectively. The cross-sectional areas of the multifidus muscles (MM) and erector spinae muscles were significantly greater in group B than in group A (P < 0.0001). However, there were no statistically significant differences in the psoas major cross-sectional areas, disc heights, and perpendicular distances between the MM and the laminae. CONCLUSIONS The MM and erector spinae muscle groups are innervated by the dorsal root of the spinal nerve arising from the same level; therefore, long-term pressure on the root caused by disc herniation can cause atrophy and degeneration of that muscle group.

Management of concomitant scoliosis and tethered cord syndrome in non-spina bifida pediatric population

BackgroundThe management of concomitant scoliosis and tethered cord syndrome in the non-spina bifida pediatric population is challenging. In the present study, we evaluate the efficacy of different treatment modalities and propose a treatment plan for the management of affected patients.MethodsA systematic literature review was conducted by querying the MEDLINE, PubMed, Cochrane, EMBASE, Scopus, and Web of Science databases for papers published between January 1996 and June 2016 and reporting on concomitant scoliosis and tethered cord. We excluded animal studies, non-English papers as well as papers reporting on patients with multiple concomitant intraspinal anomalies such as spina bifida.ResultsOut of 1993 articles, only 13 met our inclusion criteria. These 13 articles described six main management approaches: Observation, cord untethering only, cord untethering followed by deformity correction, simultaneous cord untethering and deformity correction, and deformity correction without untethering. Selection of the best approach is a function of the patient’s symptomatology and Cobb angle.ConclusionWe propose treatment plan for the management of patients with concomitant tethered cord syndrome and spinal deformity. Asymptomatic patients can be followed conservatively and managed as scoliosis patients with no need for untethering. Surgical management in a staged fashion seems appropriate in symptomatic patients with a Cobb angle less than 35°. In these patients, deformity can improve following untethering, thus sparing the patient the risks of surgical correction of scoliosis. Staged or non-staged cord untethering and curve correction seem to be adequate in symptomatic patients with Cobb angle >35° as these patients are likely to require both untethering and deformity correction.

Thoracic Epidural Hematoma Complicating Vertebroplasty

Patient: Female, 64 Final Diagnosis: Thoracic epidural hematoma Symptoms: Paraplegia Medication: — Clinical Procedure: Thoracal hemilaminectomy Specialty: Neurosurgery Objective: Diagnostic/therapeutic accidents Background: Percutaneous vertebroplasty procedures are commonly used to treat vertebral fractures. These techniques may be associated with major complications. Case Report: We present here a case of a 64-year-old female patient with T9 and T10 acute osteoporotic fractures, treated previously with vertebroplasty for four levels of osteoporotic vertebral fractures. The patient was treated by T9–T10 vertebroplasty. The post-operative neurological examination was normal. Two hours later, she progressively worsened and developed paraplegia. Magnetic resonance imaging (MRI) revealed a hyper-acute epidural hematoma over the T6 to T10 vertebrae. Evacuation of the epidural hematoma completely resolved her motor weakness. Previous literature reports one case with a thoracolumbar epidural hematoma over T11–L2 and another case with a L1 epidural hematoma after vertebroplasty. Conclusions: Percutaneous vertebroplasty is generally a safe procedure but can have rare complications. Epidural hematoma after vertebroplasty is one of the uncommon complications. Before percutaneous vertebroplasty, patients should be informed about these rare complications. Prognosis is very good if early intervention is possible.

Cauda equina cavernous hemangioma: very rare pediatric case

Dear Editor: Cavernous hemangiomas (CH) are rare vascular malformations in the central nervous system (CNS) characterized by abnormally dilated blood vessels, lined by a thin endothelium, without intervening normal nervous tissue. Intramedullary cavernomas are very rare [1]. They are usually solitary; although, they may be associated with CH in other organs or in the central nervous system. The most common clinical presentation is represented by a slowly progressive myelopathy, but subarachnoid hemorrhage and hematomyelia have also been described. The hemorrhage rate of symptomatic intramedullary CHs is 1.4–4.5% per lesion and per year [2]. A 13-year-old girl was admitted with the complaint of a 4-week history of back pain and right-side lower extremity weakness. A neurological examination revealed right extensor halluces longus (EHL) and anterior tibialis (AT) muscle weakness. Lumbar MRI revealed L1 intradural extramedullary lesion (Fig. 1a–c). We have also screened the entire neuroaxis, but we did not see any other intramedullary CH. After preoperative routine tests, we operated on the patient under general anesthesia. We excised the intradural CH after left-sided L1, L2 partial hemi-laminectomy, as described by Yasargil et al. for the removal of extramedullary and intramedullary tumors and AVMs (supplemental video file) [3]. A posterior midline longitudinal incision was made, and the subcutaneous tissues and lumbodorsal fascia of the affected side were divided. The supraspinal ligaments, interspinal ligaments, and tendinous insertions of the contralateral muscles were retained. The paraspinal muscles of the affected side were stripped, exposing the unilateral lamina to the inner edge of the articular process. Corresponding segments of the lamina were removed by a high-speed burr. Ligamentum flavum was removed and the dural sac was exposed. The oblique tilting of the operating table to the contralateral side (15–20 degrees) ensured an adequate surgical field for the procedure [3]. We used intraoperative ultrasound to localize the CH before opening the dura during surgery. Intraoperative neurophysiological monitoring was used to check nerve root potentials in order to preserve neural tissue. After opening the dura, we exposed the tumor. It was highly vascular with a prominent pulsation of the feeding arteries. The tumor was originating from a single nerve root, but it was adherent to the other cauda equina nerves. Using microneurosurgical technique under microscopic magnification, we dissected the tumor away from Electronic supplementary material The online version of this article (doi:10.1007/s00381-016-3286-9) contains supplementary material, which is available to authorized users.