The holistic approach to the CHRNA7 gene, hsa-miR-3158-5p, and 15q13.3 hotspot CNVs in migraineurs.

Migraine is a neurological disease characterized by severe headache attacks. Combinations of different genetic variations such as copy number variation (CNV) in a gene and microRNA (miRNA) expression can provide a holistic approach to the disease as a pathophysiological, diagnostic, and therapeutic target. CNVs, the Cholinergic Receptor Nicotinic Alpha 7 Subunit (CHRNA7) gene, and expression of gene-targeting miRNAs (hsa-miR-548e-5p and hsa-miR-3158-5p) in migraineurs (n = 102; with aura, n = 43; without aura, n = 59) and non-migraines (n = 120) aged 15-60 years, comparative, case-control study was conducted. Genetic markers were compared with biochemical parameters (BMI, WBC, Urea, GFR, ESR, CRP, HBG). All analyzes were performed by quantitative Real-Time PCR (q-PCR) and fold change was calculated with the 2-ΔΔCT method. The diagnostic power of the CHRNA7 gene, CNV, and miRNAs were analyzed with the receiver operating curve (ROC). CHRNA7 gene and hsa-miR-3158-5p are down-regulated in migraineurs and the gene is controlled by this miRNA via CNVs (p < .05). Both deletion and duplication were detected in patients with migraine for CVN numbers (p = .05). The number of CNV deletions was higher than duplications. When CHRNA7-CNV-hsa-miR-3158-5p was modeled together in the ROC analysis, the area under the curve (AUC) was 0.805, and the diagnostic power was "good". In migraineurs, the CHRNA7 gene can be controlled by hsa-miR-3158-5p via CNVs to modulate the mechanism of pain. These three genetic markers have diagnostic potential and may be used in antimigraine treatments.

Role of early decompressive craniectomy in traumatic brain injury: Our clinical experience.

BACKGROUND: Traumatic brain injury (TBI) is an important cause of death, especially in underdeveloped and developing countries. Diffuse edema in the damaged cerebral tissue as a result of trauma and the subsequent increase in intracranial pressure cause signifi-cant neurological deterioration. Consequently, decompressive craniectomy (DC) is performed as the surgical treatment of TBI. The aim of this study is to evaluate the post-operative mortality and morbidity rates of patients who underwent DC for TBI in our clinic. METHODS: The data of 57 cases of TBI were retrospectively analyzed. Clinical, radiological and surgical features of these cases were reviewed. The rates of mortality and morbidity, as well as main indicators of mortality were investigated. RESULTS: Twenty-five (43.8%) patients were female and 32 (56.1%) were male. The mean age was 54.5 years. Fourteen (24.5%) patients were presented with subdural hematoma, 5 (8.7%) with epidural hematoma, 18 (31.5%) with intracerebral hematoma, 13 (22.8%) with subarachnoid hemorrhage, and 7 (12.2%) with other radiological findings. DC was performed in all cases as soon as pos-sible after admission. Twelve (21.1%) patients died in the first 3 days postoperatively and 7 (12.2%) patients in the postoperative 3-15 days due to progressive cerebral damage and secondary infections. Six (10.5%) patients recovered completely and were discharged. Thirty-two (56.1%) patients were transferred to palliative care clinics and physical therapy clinics after the surgical treatment. CONCLUSION: DC, which is performed in the early period of treatment in TBI, is as important as the degree of intracerebral damage at the time of admission and the high Glasgow coma scale score. Post-operative results are more satisfactory in patients who underwent DC at an earlier stage of treatment.

Pituitary apoplexy: An emergent and potential life-threatening complication of pituitary adenomas.

BACKGROUND: Pituitary apoplexy is an emergent and potential life-threatening complication of pituitary adenomas if not managed properly. The aim of our study is to present our series of pituitary adenomas and to focus on the clinical, radiological, and surgical characteristics of this rare complication. METHODS: In this study, a total of 143 patients with pituitary adenoma underwent surgical treatment between 2016 and 2018. All patients were operated using endoscopic endonasal transsphenoidal (EET) technique. The data of pituitary apoplexy cases were recorded. Resection rates, hormonal results, and visual outcomes of patients with pituitary apoplexy were evaluated. RESULTS: Of the 143 patients, 8 (5.59%) were presented with the symptoms and radiological findings of pituitary apoplexy. The mean age was 26.75 years, and 4 (50%) of them were male and 4 were female. Pre-operative mean Knosp grading score was 2.1 All of eight patients underwent emergent surgical intervention and total resection was achieved in 75% of patients with apoplexy. Hormone levels were significantly decreased after surgery (p<0.05), except prolactin (p>0.05). Cerebrospinal fluid leakage occurred in one pa-tient. None of the patient with pituitary apoplexy died in our series. CONCLUSION: Pituitary apoplexy is an important complication of pituitary adenomas. Early diagnosis and surgical intervention provide excellent ophthalmological and hormonal outcomes. Emergent EET approach is crucial for patients with ophthalmological findings and macroadenomas.

Comparison of Different Endoscopic Techniques for the Treatment of Hydrocephalus in Children.

AIM: To present a series of hydrocephalus cases treated with different endoscopic techniques, and to compare their surgical outcomes. MATERIAL AND METHODS: Sixty-one patients underwent endoscopic approach for treating hydrocephalus over a 5-year period. Forty-six patients were children. Three surgical techniques [i.e., endoscopic third ventriculostomy (ETV), ETV plus shunting, and simultaneous ETV plus aqueductoplasty] were used in these patients. Surgical results were statistically analyzed based on age, gender, and type of surgery. RESULTS: Of the 46 children, 24 (52.17%) were female with a mean age of 25.33 months. Twenty-one (45.65%) children underwent ETV alone, 19 underwent ETV plus ventriculoperitoneal shunting, and six underwent simultaneous ETV plus aqueductoplasty. Five (10.87%) children died during the follow-up period. No correlation was observed between surgery type and patient age. No statistically significant differences in sex and complications were found between the surgical techniques. CONCLUSION: ETV alone is the safest method for treating hydrocephalus in children. Mortality is higher in patients younger than 12 months who underwent combined surgical methods, instead of ETV alone.

Screening for Copy Number Variations of the 15q13.3 Hotspot in CHRNA7 Gene and Expression in Patients with Migraines.

BACKGROUND: a migraine is a neurological disease. Copy number variation (CNV) is a phenomenon in which parts of the genome are repeated. We investigated the effects of the CNV and gene expression at the location 15q13.3 in the Cholinergic Receptor Nicotinic Alpha 7 Subunit (CHRNA7) gene, which we believe to be effective in the migraine clinic. METHODS: we evaluated changes in CHRNA7 gene expression levels and CNV of 15q13.3 in patients with migraine (n = 102, with aura, n = 43; without aura, n = 59) according to healthy controls (n = 120) by q-PCR. The data obtained were analyzed against the reference telomerase reverse transcriptase (TERT) gene with the double copy number by standard curve analysis. Copy numbers were graded as a normal copy (2), gain (2>), and loss (<2). RESULTS: we analyzed using the 2-ΔΔCT calculation method. The CHRNA7 gene was significantly downregulated in patients (p < 0.05). The analysis of CNV in the CHRNA7 gene was statistically significant in the patient group, according to healthy controls (p < 0.05). A decreased copy number indicates a dosage loss. However, no significant difference was observed among gain, normal, and loss copy numbers and expression values in patients (p > 0.05). The change in CNV was not associated with the downregulation of the CHRNA7 gene. CONCLUSION: Downregulation of the CHRNA7 gene may contribute to the formation of migraine by inactivation of the alpha-7 nicotinic receptor (α7nAChR). The association of CNV gains and losses with migraines will lead to better understanding of the molecular mechanisms and pathogenesis, to better define the disease, to be used as a treatment target.

Foramen Magnum Meningiomas: A Report of 10 Cases and Literature Review.

AIM: To present the findings and surgical results of foramen magnum meningioma surgeries performed by the authors. MATERIAL AND METHODS: Ten patients operated between 2014 and 2019 were retrospectively analyzed in terms of age, gender, neurological examination, and postoperative status. The female-to-male (F/M) ratio of the patients was 6/4, and the age range was 19?70 years (mean = 59). All patients presented with occipitocervical pain and were operated using the midline lateral suboccipital approach. RESULTS: One of the operated patients died in the intensive care unit due to upper gastrointestinal tract bleeding. Additionally, one patient had paresis in the early postoperative period, which resolved in the third follow-up month. CONCLUSION: Foramen magnum meningiomas are operated safely by microsurgical methods using the midline lateral suboccipital approach after suboccipital triangle and vertebral artery are exposed.

Preventing Sciatic Nerve Injury due to Intramuscular Injection: Ten-Year Single-Center Experience and Literature Review.

AIM: Sciatic nerve injury is the most frequent and serious complication of intramuscular gluteal injection. This study aims to highlight the incidence and causes of this continuing problem and to discuss the relevant literature. < p < MATERIAL and METHODS: A total of 217 subjects who were diagnosed with sciatic nerve injury in our neurophysiology laboratory between 2003 and 2013 were examined. Sensory and motor transmission studies and needle electromyography were performed by conventional methods in the two lower legs and the results were compared between each leg. RESULTS: Of the subjects who experienced a sciatic injury secondary to intramuscular injection, 59 (27.2%) were female and 158 (72.8%) were male. In all subjects, the dorsogluteal site of the buttocks was selected for intramuscular injection. Sciatica occurred on the right side in 91 subjects, on the left side in 125, and bilaterally in one. The peroneal nerve was more affected than the tibial nerve. The most used agents were non-steroidal anti-inflammatory drugs. According to follow-up electromyography findings of 103 subjects, significant sequelae remained in 2/3 of cases. CONCLUSION: The occurrence of sciatic neuropathy after gluteal injection causing permanent sequelae and leading to medicolegal problems is relatively rare. We suggest a double quadrant drawing technique in each gluteal region. We also draw attention to this issue with postgraduate and in-service training programs of medical staff, and providing continuity in education can reduce this serious complication.

Hypothesis: Do miRNAs Targeting the Leucine-Rich Repeat Kinase 2 Gene (LRRK2) Influence Parkinson's Disease Susceptibility?

Parkinson's disease (PD) is a frequently occurring neurodegenerative motor disorder adversely impacting global health. There is a paucity of biomarkers and diagnostics that can forecast susceptibility to PD. A new research frontier for PD pathophysiology is the study of variations in microRNA (miRNA) expression whereby miRNAs serve as "upstream regulators" of gene expression in relation to functioning of the dopamine neuronal pathways. Leucine-Rich Repeat Kinase 2 (LRRK2) is a frequently studied gene in PD. Little is known about the ways in which expression of miRNAs targeting LRKK2 impact PD susceptibility. In a sample of 204 unrelated subjects (102 persons with PD and 102 healthy controls), we report here candidate miRNA expression in whole blood samples as measured by real-time PCR (hsa-miR-4671-3p, hsa-miR-335-3p, hsa-miR-561-3p, hsa-miR-579-3p, and hsa-miR-3143) that target LRRK2. Using step-wise logistic regression, and controlling for covariates such as age, gender, PD disease severity, concomitant medications, and co-morbidity, we found that the combination of has-miR-335-3p, has-miR-561-3p, and has-miR-579-3p account for 50% of the variation in regards to PD susceptibility (p<0.0001). Notably, the hsa-miR-561-3p expression was the most robust predictor of PD in both univariate and multivariate analyses (p<0.001). Moreover, the biological direction (polarity) of the association was plausible in that the candidate miRNAs displayed a diminished expression in patients. This is consistent with the hypothesis that decreased levels of miRNAs targeting LRRK2 might result in a gain of function for LRRK2, and by extension, loss of neuronal viability. To the best of our knowledge, this is the first clinical association study of the above candidate miRNAs' expression in PD using peripheral samples. These observations may guide future clinical diagnostics research on PD.

Plasma urotensin-2 level and Thr21Met but not Ser89Asn polymorphisms of the urotensin-2 gene are associated with migraines.

BACKGROUND: Urotensin-II (U-II) is a peptide recognized by its potent vasoconstrictor activity in many vascular events, however the role of urotensin-II in migraine has not been considered yet. The molecular mechanisms and genetics of migraine have not been fully clarified yet, but it is well-known that vascular changes considerably contribute in pathophysiology of migraine and also its complications. The aim of this study was to analyze the plasma U-II levels along with genotype distributions and allele frequencies for UTS2 Thr21Met and Ser89Asn polymorphisms among the patients with migraine without aura (MWoA). METHODS: One hundred eighty-six patients with MWoA and 171 healthy individuals were included in this study. Plasma U-II levels were measured in attack free period. The genotype and allele frequencies for the Thr21Met (T21M) and Ser89Asn (S89N) polymorphisms in the UTS2 gene were analyzed. RESULTS: Plasma U-II levels were significantly higher in MWoA patients (p = 0.002). We detected a significant association between the T21M polymorphism in the UTS2 gene and migraine (53.8 % in patients, 40.4 % in controls, p = 0.035), but not with S89N polymorphism (p = 0.620). A significant relationship was found between U-II levels and MIDAS score (ß = 0.508, p = 0.001). CONCLUSION: Our study suggests that U-II may play a role in migraine pathogenesis; also Thr21Met polymorphism was associated with the risk of migraine disease. Further studies are needed for considering the role of U-II in migraine pathophysiology and for deciding if UTS2 gene may be a novel candidate gene in migraine cases.

Gene expression profiles of autophagy-related genes in multiple sclerosis.

Multiple sclerosis (MS) is an imflammatory disease of central nervous system caused by genetic and environmental factors that remain largely unknown. Autophagy is the process of degradation and recycling of damaged cytoplasmic organelles, macromolecular aggregates, and long-lived proteins. Malfunction of autophagy contributes to the pathogenesis of neurological diseases, and autophagy genes may modulate the T cell survival. We aimed to examine the expression levels of autophagy-related genes. The blood samples of 95 unrelated patients (aged 17-65years, 37 male, 58 female) diagnosed as MS and 95 healthy controls were used to extract the RNA samples. After conversion to single stranded cDNA using polyT priming: the targeted genes were pre-amplified, and 96×78 (samples×primers) qRT-PCR reactions were performed for each primer pair on each sample on a 96.96 array of Fluidigm BioMark™. Compared to age- and sex-matched controls, gene expression levels of ATG16L2, ATG9A, BCL2, FAS, GAA, HGS, PIK3R1, RAB24, RGS19, ULK1, FOXO1, HTT were significantly altered (false discovery rate<0.05). Thus, altered expression levels of several autophagy related genes may affect protein levels, which in turn would influence the activity of autophagy, or most probably, those genes might be acting independent of autophagy and contributing to MS pathogenesis as risk factors. The indeterminate genetic causes leading to alterations in gene expressions require further analysis.

Urodynamic outcomes of detethering in children: experience with 46 pediatric patients.

AIM: Tethered cord syndrome (TCS) manifests with neurological and urological complaints. Surgical detethering is the main treatment for TCS. Children with urological symptoms are required objective pre- and postoperative evaluations in order to predict urological outcome. The aims of this study are to investigate the effects of detethering procedure on the urodynamic tests and to determine the relationship between the changes of urodynamic tests and the patients' age and gender. MATERIAL AND METHODS: The data of urodynamic tests in 46 pediatric patients, who underwent surgery for TCS, were retrospectively evaluated. Bladder capacity, post-voiding residual urine volume, maximum intravesical pressure, and bladder compliance of each patient were measured in preoperative period and at the third month after surgery. These parameters were statistically compared, and the correlations of these parameters with age, gender, and etiology of the TCS were also investigated. RESULTS: Bladder capacity and post-voiding residual urine volume were decreased and maximum intravesical pressure and bladder compliance were increased after surgery for TCS. The decrease in bladder capacity was significant in patients older than 10 years (p < 0.05). The increase in maximum intravesical pressure was also positively correlated with age (p < 0.05). But the increase in bladder compliance was negatively correlated with age (p < 0.05). CONCLUSION: Bladder capacity, post-voiding residual urine volume, and bladder compliance are mainly affected by surgery in patients with TCS. From the urological viewpoint, children older than 10 years are most likely to benefit from surgery for TCS.

Oxidative stress and DNA damage in patients with migraine.

BACKGROUND: Oxidative stress is implicated in the pathogenesis of migraine, but no published studies have examined both oxidative stress levels and oxidative DNA damage on the same patient group. METHODS: In this study, total oxidant status (TOS); total antioxidant status (TAS); oxidative stress index (OSI); and 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is an indicator of oxidative DNA damage, were measured in the plasma samples of 50 prophylactic unmediated migraineurs (11 with aura and 39 without aura) and 30 matched healthy volunteers. RESULTS: No significant differences in TAS, TOS, and OSI values were observed between patients and controls. However, plasma 8-OHdG levels were found to be significantly higher in migraine patients than in the control group (p = 0.001); this increase in plasma 8-OHdG levels was more prominent in cases with migraine without aura than with aura (p = 0.001). Our results suggested an evidence of oxidative stress-related DNA damage in migraine. CONCLUSION: DNA damage reflected by plasma 8-OHdG did not studied in migraine before. Therefore, further research on oxidative stress-related DNA damage and the extent of its clinical manifestations in migraine may provide additional data to our current knowledge.

Multicentric Dentigerous Dermoid Cyst with an Unusual Location in the Central Nervous System.

Dermoid cysts are benign and congenital ectodermal inclusions. Their occurrence in an intracranial location is quite rare. They constitute 0.1 to 0.7% of all intracranial tumors. Their occurrence in the fourth ventricle and their multicentric feature are extraordinary. A 12-year-old boy was admitted to our clinic with a dermoid cyst with sixth cranial nerve involvement. He had symptoms of increased intracranial pressure. This case is the first dermoid cyst in the literature at this unusual location; a mature tooth structure was found within the cyst, which extended over the cervical subsegments. There was a second dermoid cyst in the thoracic spine (multicentric). Our aim is to present an atypical dermoid cyst along with radiodiagnostic characteristics and macroscopic findings.

Tethered cord syndrome in children: a single-center experience with 162 patients.

PURPOSE: Tethered cord syndrome (TCS) is not an uncommon clinical problem in children. The aim of this retrospective study is to document our experience on the surgical treatment of TCS in childhood. METHODS: The data of 162 children who underwent surgical treatment for TCS in a 15-year period were reviewed retrospectively. Their demographic, clinical, radiological, and surgical features were documented. They were divided into two groups as primary and secondary TCS, and the surgical technique for each group was demonstrated. Untethering the spinal cord and correction of the associated malformation were the standard surgical technique for each patient. The results of the treatment were summarized. RESULTS: Among the 162 children, 101 (62.3%) of them were female and 61 were male with a mean age of 62 months. Primary TCS was detected in 43 patients while secondary TCS was found in 119 (73.4%) patients. Hypertrichosis was the most common physical finding while back pain was the common complaint. Lipoma, split cord malformation, dermal sinus tract, and myelomeningocele were the associated malformations for secondary TCS. CONCLUSIONS: Children should be individualized for the treatment of TCS. Each patient must be evaluated neurologically and radiologically for the accurate diagnosis. Surgical untethering is the safe and effective method of treatment for children with TCS.

The Effect of Circadian Melatonin Levels on Inflammation and Neurocognitive Functions Following Coronary Bypass Surgery.

PURPOSE: In this study, the relationship between the plasma levels of melatonin and intercellular adhesion molecule-1 (ICAM-1), which plays role in several intercellular interactions including inflammatory and immune responses, and early neurocognitive functions associated with ischaemia-reperfusion injury during open heart surgery is examined. METHODS: Forty patients who were to undergo elective coronary artery bypass grafting (CABG) were divided into two groups, those who underwent their operations at 8 AM (group I; n = 20) and those who underwent their operations at 1 PM (group II; n = 20). Blood samples were collected prior to surgery (S1), when the aortic cross clamp was removed (S2) and 4 (S3) and 24 h after the surgery (S4). Neuropsychiatric assessment was conducted one day before and seven days after surgery. RESULTS: Melatonin levels measured during and after surgery were also significantly higher in Group 1. ICAM-1 levels were significantly lower in Group 1 at S2 and S3. Significant deterioration was observed in postoperative neurocognitive function compared with preoperative functions in Group 2 more than Group 1. CONCLUSION: We hypothesise that the greater preservation of neurocognitive functions in the morning patients is associated with elevated melatonin levels, which reduce the damage from ischaemia-reperfusion injury.

Early cyclosporin A treatment retards axonal degeneration in an experimental peripheral nerve injection injury model.

Injury to peripheral nerves during injections of therapeutic agents such as penicillin G potassium is common in developing countries. It has been shown that cyclosporin A, a powerful immunosuppressive agent, can retard Wallerian degeneration after peripheral nerve crush injury. However, few studies are reported on the effects of cyclosporin A on peripheral nerve drug injection injury. This study aimed to assess the time-dependent efficacy of cyclosporine-A as an immunosuppressant therapy in an experimental rat nerve injection injury model established by penicillin G potassium injection. The rats were randomly divided into three groups based on the length of time after nerve injury induced by cyclosporine-A administration (30 minutes, 8 or 24 hours). The compound muscle action potentials were recorded pre-injury, early post-injury (within 1 hour) and 4 weeks after injury and compared statistically. Tissue samples were taken from each animal for histological analysis. Compared to the control group, a significant improvement of the compound muscle action potential amplitude value was observed only when cyclosporine-A was administered within 30 minutes of the injection injury (P < 0.05); at 8 or 24 hours after cyclosporine-A administration, compound muscle action potential amplitude was not changed compared with the control group. Thus, early immunosuppressant drug therapy may be a good alternative neuroprotective therapy option in experimental nerve injection injury induced by penicillin G potassium injection.

Investigation of the Plasma Nitrite Levels and Oxidant-Antioxidant Status in Obstructive Sleep Apnea Syndrome.

INTRODUCTION: Obstructive sleep apnea (OSA) is one of the most prevalent sleep disorders. In the present study, we assessed the nitrite level, which is an indirect indicator of nitric oxide (NO), total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI), which may be associated with endotel dysfunction. We investigated the difference between the groups and the relationship among the severity of comorbid conditions. METHODS: This study was conducted in 39 OSA patients confirmed by polysomnography and 40 healthy subjects (controls). The OSA group consisted of 10 women and 29 men and the control group consisted of 20 women and 20 men. Polysomnographic revealed mild OSA in two, moderate in 7 and severe in 30 cases. We measured plasma TAS, TOS and nitrite levels from venous blood. The OSI value was obtained by dividing the TOS and TAS values. Values were compared with the control group and between patient groups. RESULTS: A high body mass index (BMI), cardiovasculer diseases (CVD) and the use of medication for co-morbid diseases were more prevalent in the OSA group (p=.001, p=.029 and p=.006, respectively). The median plasma TOS level and OSI in the obstructive sleep apnea syndrome (OUA) group were significantly higher than those in the control group (p=.001 and p=.001, respectively). The plasma median nitrite level and TAS did not show any significant difference between the OSA and the control groups. None of the parameters revealed a significant difference between severe and moderate OSA cases. CONCLUSION: Our findings in the present study revealed that the oxidant-antioxidant balance shifted toward the oxidant side in OSA cases; however, the NO level did not change. These findings together may point out that some molecules other than NO may have a role in the pathophysiology of endothelial dysfunction and also in the disturbed oxidant-antioxidant balance in OSA.