Cerebrolysin provides effective protection on high glucose-induced neuropathy in cultured rat dorsal root ganglion neurons.

Cerebrolysin, an endogenous peptide with neuroprotective and neurotrophic properties, indicated to be beneficial on diabetic neuropathy by preliminary clinical and experimental studies but without evidence on central or peripheral action. Dorsal root ganglion (DRG) neurons, based on involvement of pain sensation in both health and disease as first relay centers for transmission and processing of peripheral nociceptive sensory signals, was used to investigate possible effects of Cerebrolysin on high glucose-induced neuropathy, as model. DRG's were obtained from adult rats and the isolated neurons were seeded on E-Plate®'s equipped with gold microelectrodes, and incubated in culture media in a CO2 incubator at 37 C. DRGs were exposed to high glucose (50 mM) in the absence and presence of different concentrations of Cerebrolysin ® (2-40 mg/ml). Cell index (derived from cell viability and neurite outgrowth) was recorded with Real-Time Cell Analyzer and was used as primary outcome measure. High glucose-induced cellular neuropathy and neuroprotective effects of Cerebrolysin was evaluated from area under the curve (AUC) of cell index-time graphs. Exposure of DRG neurons to high glucose caused a rapid and persistent decrease in the mean AUC values compared to normoglycemic controls. Co-treatment with Cerebrolysin (40 mg/ml) attenuated this high glucose-induced effect in a concentration-dependent manner. In normoglycemic conditions, treatment with Cerebrolysin caused a dose-dependent increase in the mean AUC values. Cerebrolysin treatment resulted in maintenance of the functional integrity, survival, and promotion of neurite outgrowth of the cultured DRG neurons exposed to high glucose, indicating involvement of peripheral sensory neurons.

Cortexin® Ameliorates High Glucose-Induced Neuropathy in Cultured Rat Sensory Neurons.

INTRODUCTION: The aim of this study was to investigate whether Cortexin®, a brain peptide-containing agent, has any mitigating effect on high glucose-induced neuropathy, using primary cultured rat sensory neurons. MATERIALS AND METHODS: Dorsal root ganglia (DRG) were excised from decapitated adult rats. Individual neurons were isolated following enzymatic and mechanical procedures. Cells were seeded on E-plate® with gold microelectrodes and maintained in conventional culture media in a CO2 incubator at 37°C. After allowing for 24 h for cell adhesion and recovery from acute enzymatic trauma, neurons were exposed to high glucose (HpG) in the absence and presence of different concentrations of Cortexin® (2-40 µg/mL). Neuroprotective effects were followed with the Real-Time Cell Analyzer® by utilizing measurement of Cell Index, a parameter representing cell viability, cell attachment, and neurite outgrowth. RESULTS: Exposure of DRGs to HpG (50 mm) caused a rapid and sustained decrease in the mean area under the curve (AUC, values derived from time vs. Cell Index curve) compared to the mean AUC values in normoglycemic (NG) wells. Co-treatment with Cortexin® attenuated this HpG-induced effect, in a concentration-dependent manner (NG: 1.00 ± 0.00 vs. HG: 0.18 ± 0.02, p < 0.05; and HpG + Cortexin® [40 µg/mL]: 0.66 ± 0.17, p = 0.002 versus HpG). In normoglycemic conditions, Cortexin® treatment led to a concentration-dependent increase in the mean AUC values. CONCLUSIONS: Data from this in vitro study suggest that Cortexin® has potential neuroprotective effects against chronic hyperglycemic insult in rat sensory neurons. Our results warrant further in vivo studies and may have clinical implications for diabetes-associated peripheral neuropathy.

Subdural empyema in immunocompetent pediatric patients with recent SARS-CoV-2 positivity: case report.

Subdural empyema refers to the collection of purulent material in the subdural space and the most source of it is bacterial meningitis in infants while sinusitis and otitis media in older children. It has been very recently reported that coronaviruses (CoV) exhibit neurotropic properties and may also cause neurological diseases. CoV-related complications as hypercoagulability with thrombosis and associated inflammation, catastrophic cerebral venous sinus thrombose sand bacterial-fungal superinfections have been well documented in adult patients. Hereby, we describe 15-year-old and 12-year-old female children with subdural empyema after SARS-CoV2. The patients presented limitation of eye in the outward gaze, impaired speech, drowsiness, fever, vomiting and they also were tested positive for COVID-19. MRI indicated subdural empyema and surgical interventions were needed to relieve intracranial pressure and drain pus after receiving broad spectrum antibiotics treatments. The microbiological analysis of abscess material revealed Streptococcus constellatus which is extremely rare in an immunocompetent child and the patients received appropriate IV antibiotic therapy. Eventually, patients became neurologically intact. Pediatric patients with CoV infections should be closely monitored for neurological symptoms. Further research and more data on the correlation between CoV infections would provide better recognition and treatment options in an efficient manner in children.

Interesting negative correlation between transorbital optic nerve sheath diameter and Evans' index values; can it be predictive for failure of endoscopic third ventriculostomy?

Background: Currently, Endoscopic third ventriculostomy (ETV) is one of the commonly used surgical options for the treatment of non-communicating hydrocephalus but reported success rates from ETV vary considerably, and a reliable noninvasive means to detect the efficacy of ETV is still lacking. In this study, the changes in Evans's Index and the transorbital optic nerve sheath (ONSD) diameter measurement after endoscopic third ventriculostomy were compared. Methods: Preoperative and early postoperative ultrasonographic ONSD measurement and preoperative and postoperative 3 months Evans' index of patients with hydrocephalus on whom ETVs were performed between 1 February 2018 and 23 May 2022 and analyzed. Results: The chart of 8 male and 2 female patients was analyzed. Their median age at presentation was 5.3 years (range 1 - 14 years). Mean ONSD values were 5.66 mms in the preoperative period, which was decreased to a mean of 4.17 mms in the early postoperative period. The Evans' index was 0.5320 in the preoperative period; however, it decreased to 0.4460 in the postoperative 3rd months. The preoperative and early postoperative mean ONSD values and Evans' Index of patients were significantly different. Interestingly, a negative correlation was also observed between ONSD values and Evans' index. Conclusions: ONSD measurement and Evans' index have been commonly used after ETV procedures In pediatric patients with hydrocephalus. Still, there is an unexplained negative correlation between ONSD and Evans' index values. This study indicates that the two measures (Evans's index and ONSD) should be considered when performing follow-up examinations in patients after ETV.

Penetrating craniocerebral nail gun injury in a child: a case report.

Penetrating craniocerebral injuries with a nail gun are extremely rare and even rarer in children. In this case, a 2-year-old boy, who was the youngest patient in the literature with an intracranial nail gun injury involving penetration of the right temporal lobe, was reported. The patient was evaluated by plain radiography and computed tomography. The nail was loosened and pulled gently out by creating a small craniotomy around the nail entrance. Although clinical characteristics and treatment methods of penetrating craniocerebral injuries were similar for reported in literature, the injury mechanism of presented case was different. Penetrating craniocerebral injuries with a nail gun are very dramatic situation, but mortality and morbidity are low. Without major vascular injury, a nail can be removed through a small incision. Penetrating injuries often occur accidentally in the pediatric age group, but the risk of child abuse should always be considered.

The Effect of Neuroscientists on the Studies of Autonomic Nervous System Dysfunction Following Experimental Subarachnoid Hemorrhage.

OBJECTIVE: The autonomic nervous system dysfunctions following subarachnoid hemorrhage (SAH) are common in neurosurgical clinical practice. The aim of the study is to investigate the effect of Asian neuroscientists on the studies of autonomic nervous system dysfunction following experimental subarachnoid hemorrhage. METHODS: A systematic search was conducted using the MEDLINE and Web of Science databases for studies pertaining to SAH and autonomic nervous system dysfunction. The searched terms contained "experimental subarachnoid hemorrhage," "autonomic nervous system," and "Ganglion." RESULTS: There are many animal studies because the live human brain vessels cannot be used in investigations. The considerable efforts have been made to investigate the effect of SAH on the autonomic nervous system in laboratory animals. Seventy-four studies were published by various authors. Most of the articles came from Asian Countries 49 studies (66.2% of the total studies). The most preferred animals were rabbits (in 43 studies, 58.1% of the total studies). CONCLUSION: Asian neuroscientists published enormous contributions in SAH-related autonomic nervous system dysfunction. It was shown that there is a great interest of Asian neuroscientists for autonomic nervous system changes secondary to SAH.

An Acute Complication of Ventriculoperitoneal Shunt with Bladder Perforation and Extrusion through the Urethra in a Newborn: Case Report and Review of the Literature.

Ventriculoperitoneal shunt (VPS) surgery is a standard procedure for the management of hydrocephalus. Bladder perforation is an extremely rare complication of VPS surgery. Herein, we present for the first time an acute complication of VPS with bladder perforation and extrusion through the urethra in a newborn. We also reviewed the complication of VPS with bladder perforation as reported in the literature.

Paradox in the cubital tunnel syndrome--frequent involvement of left elbow: first report.

OBJECTIVE: Cubital tunnel syndrome (CuTS) is the second most common compression neuropathy in the arm, but the existence of a compressive cause has not been determined conclusively and the majority of the cases are idiopathic. In this paper, involvement sides of limbs of patients with cubital tunnel syndrome were studied. MATERIAL AND METHODS: Between October 2008 and December 2011, the clinical assessment of consecutive operated patients with cubital tunnel syndrome in Rize Education and Research Hospital were analysed. The diagnosis and severity of syndrome was based on electro-diagnostic study. RESULTS: This study included 57 consecutive patients with cubital tunnel syndrome (39 men, 18 women; mean age, 44,7 years; range, 23-79 years; mean age, 44,7 years; range, 23-79 years); 31 patients underwent surgical treatment. Involvement was on the right side in 18 and on the left in 39 patients. Severity scores and MCV were statistically significant between sides. CONCLUSION: Profound involvement with cubital tunnel was found in left elbow. According to the finding of non-dominant elbow involvement in our study, the exact etiology and ideal management of cubital tunnel syndrome continues to be heavily debated.

Erdheim-Chester disease misdiagnosed as meningioma of the pontocerebellar angle: A case report and review of literature.

Erdheim-Chester Disease (ECD) is a rare non-Langerhans form of systemic histiocytosis of unknown etiology with multiple organ involvement. It most commonly affects the long bones, lungs, heart, retroperitoneum, eyes, and kidneys and less commonly the brain and spinal cord. Although there are very few cases of supratentorial ECD mimicking intracranial meningioma reported in literature, to the best of our knowledge, there are no reports on ECD mimicking infratentorial pontocerebellar angle meningioma. The present study reports a case of ECD mimicking pontocerebellar angle meningioma. This study aimed to emphasize the importance of systemic evaluation using a multidisciplinary approach as well as the need for considering ECD as a differential diagnosis of xanthomatous meningioma.

Age- and gender-related radiological changes of the cervical spine: A study with largest magnetic resonance imaging database of 5672 consecutive patients.

Background: The morphological features of the cervical spine are an essential issue. This retrospective study aimed to investigate the structural and radiological changes in the cervical spine. Materials and Methods: A total of 250 patients with neck pain but no apparent cervical pathology were selected from a database of 5672 consecutive patients undergoing magnetic resonance imaging (MRI). MRIs were directly examined for cervical disc degeneration. These include Pfirrmann grade (Pg/C), cervical lordosis angle (A/CL), Atlantodental distance (ADD), the thickness of transverse ligament (T/TL), and position of cerebellar tonsils (P/CT). The measurements were taken at the positions of T1- and T2-weighted sagittal and axial MRIs. To evaluate the results, patients were divided into seven age groups (10-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70, and over). Results: In terms of ADD (mm), T/TL (mm), and P/CT (mm), there was no significant difference among age groups (P > 0.05). However, in terms of A/CL (degree) values, a statistically significant difference was observed among age groups (P < 0.05). Conclusions: Intervertebral disc degeneration was more severe in males than in females as age increased. For both genders, cervical lordosis, decreased significantly as age increased. T/TL, ADD, and P/CT did not significantly differ with age. The present study indicates that structural and radiological changes are possible reasons for cervical pain at advanced ages.

An investigation of the effects of chronic zonisamide, sultiam, lacosamide, clobazam, and rufinamide anti-seizure medications on foliculogenesis in ovarian tissue in prepubertal non-epileptic rats.

We aimed to determine the morphological and histological effects of zonisamide, sultiam, lacosamide, clobazam, and rufinamide on ovarian folliculogenesis in rats. Sixty female Wistar rats were divided into six experimental groups as control, zonisamide, sultiam, lacosamide, clobazam, and rufinamide groups; control solution and drugs were administered by gavage for 90 days. The number of healthy follicles in the control group was significantly higher than in the anti-medication groups (p < 0.001), and the number of corpus luteum was significantly lower (p < 0.001). There was a significant difference in the number of TUNEL positive apoptotic follicles between the control and drug groups (p < 0.001). With EGF, IGF-1, and GDF-9 staining, a very strong immunoreaction was observed in the ovarian multilaminar primary follicle granulosa cells and oocytes in the control group compared to the drug group (p < 0.001). Long-term anti-seizure medication with zonisamide, sultiam, lacosamide, clobazam, and rufinamide from prepubertal to adulthood causes apoptosis and disruption of folliculogenesis in the ovarian follicles of nonepileptic rats.

One of the giants of neurological surgery left us more than a decade ago, and neurosurgical literature did not show much interest.

One of the giants of neurological surgery left us over a decade ago. Charles George Drake died September 15, 1998 in London, Ontario after an extended bout with lung cancer. Although he will always be identified with taking posterior fossa aneurysm surgery from the realm of the daring to the domain of the routine, his contributions were much broader. Clinical neurosciences have been blessed in the past century by the life and works of Drake. In the neurosurgical world, the achievements of Drake are very well known and have been well recorded. Unfortunately, in the past decade since his passing, only one paper has been published about him and his contributions to neurosurgery. This is a historical paper regarding Charles George Drake that attempts to (1) remember Drake as a pioneer; (2) to evaluate lessons that we have learned from him; and (3) to address the question 'What made him great?'. As per Drake's teachings, this paper is meant to articulate the unique perspectives Charlie provided with respect to how we learn our craft, maintain the integrity of reporting, and implement suggestions as to how we may progress into the future. In conclusion, it is our hope that this paper will bring to life the unique character of Drake and his unprecedented blend of genius, creativity, technical skill, introspection, and ever-present humility for all international neurosurgeons to appreciate.

What makes Maurice Ravel's deadly craniotomy interesting? Concerns of one of the most famous craniotomies in history.

Maurice Ravel (1875-1937), the great impressionist-classicist composer of many popular compositions, such as the Boléro, suffered from a progressive disease and died following an exploratory craniotomy by Clovis Vincent. The history of his progressive dementia and the contribution of a car accident, following which he was unable to function, have received a certain amount of interest in the neurological literature previously, but his deadly craniotomy was not evaluated from a neurosurgery perspective. The car accident in 1932, with the probable consequence of a mild-to-moderate traumatic brain injury, could be the key event in his life, triggering the loss of his ability to compose. It is clear that he never recovered from his injury and within a year he became completely unable to function. His dementia progressed dramatically. This event needs to be kept in mind. In 1937, Ravel died after the craniotomy performed by Vincent, but only a speculative, retrospective diagnosis is possible since an autopsy was not undertaken.

Electrophysiological, functional and histopathological assessments of high dose melatonin on regeneration after blunt sciatic nerve injury.

The aim of this study was to determine the curative effects of high-dose (100 mg/kg) melatonin on peripheral nerve injury. Forty male Wistar albino rats were randomized into four groups as sham, vehicle, melatonin, and ischemia and their right sciatic nerves were exposed. The process was terminated in the sham group. In the other groups, nerve injury was induced by clip compression. The vehicle group was intraperitoneally administered ethanol 0.1 cc (melatonin solvent), while the melatonin group was intraperitoneally administered a single dose of melatonin (100 mg/kg). Following the surgery, sciatic nerve functional index (SFI) was measured using walking track analysis on days 7, 14, and 21, and latency, amplitude, and muscle action potentials (MAP) field values were measured using electroneuromyography (ENMG) on day 21. Histopathologically, edema, axonal degeneration, myelin damage, and inflammatory response were evaluated in all groups. SFI values were noted to be statistically significantly different among the vehicle, melatonin, and ischemia groups, and the melatonin group showed a faster recovery. In the ENMG evaluations, higher amplitude and field values in the melatonin group indicated that melatonin accelerated peripheral nerve recovery. Histopathologically, although fibers with loss of myelin were identified in the melatonin group, the myelin sheath was preserved in general and the axonal structure was noted to be normal. A single injection of high-dose melatonin was found to preserve myelin sheath, prevent axonal loss, and accelerate functional recovery during the nerve regeneration in peripheral nerve injury.

Neurosurgery is a profession.

At present, the rapid advances in neurosurgical knowledge and technology are putting increased pressure on neurosurgeons to process huge quantities of information, with requirements for continuous learning and updating knowledge and skills which are time-consuming but essential. All these changes to the venerated status quo of neurosurgical practice have created an environment that may have a negative impact on neurosurgical professional behaviour. As a result, it may be that neurosurgeons find it increasingly difficult to meet their responsibilities to patients. In these circumstances, reaffirming the fundamental and universal principles and values of neurosurgical professionalism, which remain ideals to be pursued by all neurosurgeons, becomes all the more important. This paper summarizes the definition, evolution, and practice of neurosurgical professionalism.

Xanthomatous Meningioma: A Case Report.

Meningioma is a neoplasm derived from meningothelial cells. Grade1 meningiomas consist of 9 different subtypes. One of the rare subtypes is metaplastic meningioma. Metaplastic meningioma could be defined as "xanthomatous meningioma" in the presence of prevalent xanthomatous changes. A 32-year-old male patient presented to the outpatient clinic with complaints of vertigo and tinnitus. Magnetic resonance imaging revealed a large mass lesion of 7.4 cm in the right frontal region with an extra-axial localization. Resection material demonstrated a neoplasm composed of classical meningothelial meningioma areas accompanied with areas of xanthomatous changes, containing cells with clear, vacuolated cytoplasm. Epithelial membrane antigen (EMA), vimentin, and progesterone expression were evident in both xanthomatous and meningothelial meningioma areas. Additionally, CD68 positivity was also observed in xanthomatous areas. EMA positivity is a neoplastic marker for xanthomatous cells and is a critical marker to differentiate these cells from macrophages, which is crucial for pathologists in the differential diagnosis. Xanthomatous meningiomas are quite rare and our case presentation is the 7 < sup > th < /sup > one in the current literature.

Whole Brain Radiotherapy Plus Conventional Boost in Non-Small Cell Lung Cancer Patients with Brain Metastasis: A Retrospective Analysis of Overall Survival.

AIM: To evaluate the clinical characteristics and treatment outcomes of non-small cell lung cancer (NSCLC) patients with brain metastasis, who were treated by whole brain radiotherapy with a conventional boost at a single institution. MATERIAL AND METHODS: A total of 296 patients diagnosed with NSCLC with brain metastasis and referred to our clinic for radiotherapy between 2000 and 2017 were included in this retrospective study. RESULTS: The median age was 60.8 ± 12.1 years, with a range of 21-85 years. The estimated median survival time for all patients was 7.81 ± 0.66 months (95% CI: 6.52-9.11). The one-year survival, two-year survival and three-year survival rates were 18.8%, 5.8% and 2.9%, respectively. The median survival of patients with solitary brain metastasis who received 45 Gy radiotherapy was 14.70 ± 2.80 months (95% CI: 9.20-20.20). These patients had 6 and 12 months survival rates of 65.4% and 42.6%, respectively. The median survival time of patients with solitary brain metastasis who received > 45 Gy radiotherapywas 13.86 ± 2.56 months (95% CI: 8.08-18.02). These patients had 6 and 12 months survival rates of 66.2% and 27.2%, respectively. There was no significant difference between the two groups (p=0.321). The median survival duration of patients under 65 years was 9.65 ± 1.02 months. The median survival time of patients aged 65 years and overwas 5.15 ± 0.51 months. There was a statistically significant difference in the median survival rates between the groups (p < 0.001). CONCLUSION: Patients with solitary metastasis or single metastases tolerated whole brain radiotherapy with a conventional boost. Although the overall survival rates were numerically better in the high dose RT group, the difference was not statistically significant. Prospective studies with a larger sample size are needed to consolidate our results.

Vitamin D protects against hippocampal apoptosis related with seizures induced by kainic acid and pentylenetetrazol in rats.

OBJECTIVES: The hippocampus is susceptible to damage in patients with epilepsy and in animals with seizures caused by excitotoxic agents. The effect of vitamin D on hippocampal apoptosis related with seizures has not been reported. However, epileptic patients have an increased risk of hypovitaminosis D which is most likely due to the effects of antiepileptic drugs. Therefore, in this study, it was aimed to evaluate the effects of vitamin D on hippocampal apoptosis related with seizures by using pentylenetetrazol (PTZ) and kainic acid (KA) in rats. METHODS: Male Sprague Dawley rats, aged 5.5 weeks, were randomly divided into six groups: control, vitamin D, PTZ, KA, PTZ + vitamin D and KA + vitamin D groups. The groups that received vitamin D were given 500 IU/kg of vitamin D daily for two weeks in addition to a standard diet. At the end of this period, PTZ and KA were applied to trigger seizures in the rats in the seizure groups. 24 h after the administration of PTZ and KA, the rats were decapitated. In the hippocampal region, apoptosis was assessed by TUNEL and brain-derived neurotrophic factor (BDNF), Bax, caspase-3 and c-fos activation were evaluated by immunohistochemical method. RESULTS: BDNF level increased while c-fos, Bax and caspase-3 levels decreased (p < 0.0001, in all) in the hippocampal neurons of the groups that were pre-treated with vitamin D before the administration of PTZ and KA, in comparison with the PTZ and KA groups. Vitamin D significantly decreased the number of apoptotic cells in these rats in comparison with the PTZ and KA groups (p < 0.0001). CONCLUSION: This study indicates that vitamin D has neuroprotective effects on hippocampal apoptosis induced by PTZ and KA in rats. With this study it is suggested that keeping vitamin D levels within normal limits may be beneficial for patients with epilepsy, especially children.

Neglected knowledge: Asymmetric features of lumbar disc disease.

BACKGROUND: Lumbar disc herniations have been extensively studied in the literature. Asymmetric trunk muscle anatomy could affect the development of this entity which has never been quantitatively studied previously. The purpose of this manuscript was to analyze the operated sides of herniated lumbar disc. MATERIALS AND METHODS: Data files of patients with lumbar disc herniation operated in author's hospital between January 2007 and March 2009 were analyzed. RESULTS: In operated side analysis, discectomy side was 53% on the left side, 40% on the right side, the difference between two sides was statistically significant. CONCLUSION: The asymmetric distribution may be a significant factor in the development and surgical treatment of lumbar disc herniations.

Sudden death and cervical spine: A new contribution to pathogenesis for sudden death in critical care unit from subarachnoid hemorrhage; first report - An experimental study.

CONTEXT: Sudden death from subarachnoid hemorrhage (SAH) is not uncommon. AIMS: The goal of this study is to elucidate the effect of the cervical spinal roots and the related dorsal root ganglions (DRGs) on cardiorespiratory arrest following SAH. SETTINGS AND DESIGN: This was an experimental study conducted on rabbits. MATERIALS AND METHODS: This study was conducted on 22 rabbits which were randomly divided into three groups: control (n = 5), physiologic serum saline (SS; n = 6), SAH groups (n = 11). Experimental SAH was performed. Seven of 11 rabbits with SAH died within the first 2 weeks. After 20 days, other animals were sacrificed. The anterior spinal arteries, arteriae nervorum of cervical nerve roots (C6-C8), DRGs, and lungs were histopathologically examined and estimated stereologically. STATISTICAL ANALYSIS USED: Statistical analysis was performed using the PASW Statistics 18.0 for Windows (SPSS Inc., Chicago, Illinois, USA). Intergroup differences were assessed using a one-way ANOVA. The statistical significance was set at P < 0.05. RESULTS: In the SAH group, histopathologically, severe anterior spinal artery (ASA) and arteriae nervorum vasospasm, axonal and neuronal degeneration, and neuronal apoptosis were observed. Vasospasm of ASA did not occur in the SS and control groups. There was a statistically significant increase in the degenerated neuron density in the SAH group as compared to the control and SS groups (P < 0.05). Cardiorespiratory disturbances, arrest, and lung edema more commonly developed in animals in the SAH group. CONCLUSION: We noticed interestingly that C6-C8 DRG degenerations were secondary to the vasospasm of ASA, following SAH. Cardiorespiratory disturbances or arrest can be explained with these mechanisms.