Search

Glioblastoma (GBM) treatment is extremely challenging due to the high complexity of the tumor. It is one of the tumors in which a subpopulation of highly resistant glioma initiating cells (GICs) has been clearly identified. Thus, understanding the differences between GICs and tumor bulk cells is therefore essential to move to less conventional but more efficient approaches. It was found that, unlike their differentiated progeny, GICs survival and maintenance of stem cell properties depend on mitochondrial metabolism. GICs present higher glucose uptake and mitochondrial membrane potential and reduced lactate dehydrogenase activity, being more sensitive to mitochondrial inhibition than their differentiated counterparts. Calcium flux to the mitochondria appears to play an essential role in the maintenance of this distinct metabolic phenotype with a decrease in the expression of voltage‑dependent anionic channel (VDAC) and Grp75, two of the proteins of the IP3R‑Grp75‑VDAC complex that transfers calcium from the endoplasmic reticulum (ER) to the mitochondria. Disruption of ER homeostasis using ER stress inducers or inhibition of ER‑mitochondrial contact sites using the Grp75 inhibitor MKT‑077 resulted in cytotoxicity of GICs and loss of stemness. Moreover, MKT‑077 also potentiates the effect of temozolomide, current treatment for glioblastoma. In summary, the present data indicated that ER‑mitochondrial homeostasis is essential for regulation of GICs glucose metabolism and survival.

Introduction: Cerebral swelling often occurs during craniotomy for cerebral tumors. Poor brain relaxation can increase the risk of cerebral ischemia, possibly worsening the outcome. The surgical team should identify any risk factors that could cause perioperative brain swelling and decide which therapies are indicated for improving it. The present investigation aimed to elucidate the risk factors associated with brain swelling during elective craniotomy for supratentorial brain tumors., Methods: This prospective, nonrandomized, observational study included 52 patients scheduled for elective supratentorial tumor surgery. The degree of brain relaxation was classified upon the opening of the dura according to a four-point scale (brain relaxation score: 1, perfectly relaxed; 2, satisfactorily relaxed; 3, firm brain; and 4, bulging brain). Moreover, hemodynamic and respiratory parameters, arterial blood gas, and plasma osmolality were recorded after the removal of the bone flap., Results: This study showed that the use of preoperative dexamethasone was associated with a brain relaxation score of ≤2 (p = 0.005). The median midline shift of 6 (3-0) mm and median hemoglobin level of >13 g/dL were associated with a brain relaxation score of ≥3 (p = 0.02 and p = 0.01, respectively). The dosage of mannitol (0.25 g/kg   versus 0.5 g/kg), physical status, intraoperative position, tumor diameter and volume, peritumoral edema and mass effect, World Health Organization (WHO) grading, mean arterial pressure, PaCO 2 , osmolality, and core temperature were not identified as risk factors associated with poor relaxation., Conclusion: The use of preoperative dexamethasone was associated with improved brain relaxation, whereas the presence of a preoperative midline shift and a higher level of hemoglobin were associated with poor brain relaxation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Pérez de Arriba et al.)

Introduction The use of orthopedic implants is a cause for concern for the release of its integrating metals and the systemic complications that may occur. Instrumented spine arthrodesis is the recommended treatment for many spine diseases. Different segmental fixation devices, commonly made of titanium and its alloys, are used in these surgeries. The use of this metal for spinal fusion has introduced the possibility of generating microscopic metal particles that are present in the tissues of the surrounding implants (peri-implant environment). In fact, metal debris has been found in the paraspinal soft tissues of patients with posterior lumbar instrumentation and showed to be particularly high in patients undergoing revision procedures of pseudoarthrosis. In addition, part of the metals might also dissolve (either from the released particles or directly from the implant surface) and circulate in the body fluids, accumulating (eventually) in remote organs. Material and methods A prospective study was designed with patients who were to be operated by the pathology of the lumbar spine to perform a vertebral arthrodesis composed of a titanium alloy (n=32). Two subgroups were differentiated according to the type of surgery performed: a) Posterolateral arthrodesis (N=5); b) Circumferential arthrodesis intervertebral implant of polyester-ether ketone (PEEK) (N=8) or titanium (N=19). The blood sample was taken before surgery and one year later. The samples were analyzed by mass spectrophotometry with a double focus inductive coupling plasma source (DF-ICP-MS). Results Blood titanium levels prior to surgery were similar to those in other publications (0.7449 micrograms per liter -1  (µgL -1 ), Standard Deviation (SD)=0.562). The average titanium concentration levels found after surgery was 2.5406 µgL -1  (SD=3,69), near 3.5-fold increase. After surgery, there was a significant mean increase in serum titanium levels of 1.7957 µgL -1  (SD=3.5765, Range=-0.57 µgL -1 ; 14.60 µgL -1 ). There is a statistically significant increment (p=0.00049) of the titanium concentration in the serum of the patients after surgery. If we analyze the patients in three groups according to the type of implants used (posterolateral, circumferential with PEEK, and circumferential with titanium), there are no differences between those who did not have an intersomatic device implanted and those in which PEEK implants were implanted, but with those in which it was titanium it was p=0.006 and p=0.018, respectively. Conclusions Patients undergoing vertebral instrumentation experience a significant increase in serum titanium levels compared to before surgery levels. The use of an intersomatic device did not show differences in titanium release with not using it when it was PEEK. There are significant differences between patients without intersomatic implants or those who had a PEEK implant with those in whom it was titanium, with a significant increase in blood titanium levels., Competing Interests: The authors have declared that no competing interests exist.

Background: Deep brain stimulation (DBS) and the proper target for chronic cluster headache (CCH) are still subjects of controversy., Objectives: We present our long-term results of analysis of the target and its structural connectivity., Methods: Fifteen patients with drug-resistant CCH underwent DBS in coordinates 4 mm lateral to the III ventricular wall and 2 mm behind and 5 mm below the intercommissural point. The clinical parameters recorded were the number of weekly attacks, pain intensity, and duration of the headache. Structural connectivity was studied using 3-T MR diffusion tensor imaging (DTI)., Results: All of our patients improved from a mean of 39 attacks/week to 2; pain intensity decreased from 9 to 3 out of 10, and the mean cephalalgia duration decreased from 53 to 8 min. The mean stereotactic coordinates of the effective contact location were 6.1 mm lateral to the midcommissural point and 1.2 mm behind and 4.0 mm below the intercommissural point. DTI analysis showed that this target was connected to tracts and nuclei of the posterior mesencephalic tegmentum, specifically the dorsal longitudinal and mamillotegmental fasciculi., Conclusions: Our data showed DBS to be a safe and useful procedure for the treatment of drug-resistant CCH; the rate of improvement was higher than those found in other series. Although these are promising results, larger series targeting those fasciculi with a longer follow-up are needed., (© 2018 S. Karger AG, Basel.)

The occurrence of brain tumors together with aneurysms has been considered as an uncommon phenomenon. However, its incidence may be underestimated. This coexistence is a diagnostic challenge, but also a therapeutic one as no consensus has been reached. We report two cases of a 71 and 67 years old patient with a meningioma and aneurysm: one noticed and treated before with good outcome and the other without treatment before surgery with fatal outcome. The different outcome of these patients shows the importance of vascular study in surgical planning. Treatments options are changing and although some authors think the pathology that causes symptoms should be treated first, endovascular treatment of the aneurysm is a safe option to prevent aneurysm rupture during surgery.

Glioblastoma-initiating cells (GICs) represent a stem cell-like subpopulation within malignant glioblastomas responsible for tumor development, progression, therapeutic resistance, and tumor relapse. Thus, eradication of this subpopulation is essential to achieve stable, long-lasting remission. We have previously reported that melatonin decreases cell proliferation of glioblastoma cells both in vitro and in vivo and synergistically increases effectiveness of drugs in glioblastoma cells and also in GICs. In this study, we evaluated the effect of the indolamine alone in GICs and found that melatonin treatment reduces GICs proliferation and induces a decrease in self-renewal and clonogenic ability accompanied by a reduction in the expression of stem cell markers. Moreover, our results also indicate that melatonin treatment, by modulating stem cell properties, induces cell death with ultrastructural features of autophagy. Thus, data reported here reinforce the therapeutic potential of melatonin as a treatment of malignant glioblastoma both by inhibiting tumor bulk proliferation or killing GICs, and simultaneously enhancing the effect of chemotherapy., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Several surgical adverse events (SAEs) have been associated with Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's Disease (PD) patients, leading to certain confusion about the risk/benefit ratio of this technique, and giving rise to the need of more and more extensive control studies over longer periods. The aim of this article is to identify and quantify the factors associated with the most frequent AEs from STN DBS in PD-diagnosed patients., Methods: The following variables were studied: aborted procedure, misplaced leads, intracranial haemorrhage, and seizures. This study was carried out in 233 patients diagnosed with PD, with 455 STN electrodes implanted and follow-up after 7 (8-14) years follow up., Results: A total amount of 56 SAEs occurred in 49 patients (11.76 % of total procedures, 12.31 % of implanted leads, 21.03 % of patients). SAEs were: five aborted procedures, 26 misplaced leads, ten intracranial haemorrhages, and 15 seizures. Of all the SAEs, long-term effects only happened in two cases of hemiparesis caused by intracranial haemorrhage; the other SAEs were reversible and didn't leave any long-term clinical consequences (0.42 % of procedures, 0.44 % of leads, and 0.86 % of patients)., Conclusions: STN DBS in PD patients is a safe surgical procedure, with good risk/benefit ratios: procedure reliability/correct lead implantation in 95.59 %, 0 mortality/implanted lead, 0.12 morbidity/implanted lead, and 0.0043 neurological sequelae/implanted lead.

Background: Current evidence indicates that a stem cell-like sub-population within malignant glioblastomas, that overexpress members of the adenosine triphosphate-binding cassette (ABC) family transporters, is responsible for multidrug resistance and tumour relapse. Eradication of the brain tumour stem cell (BTSC) compartment is therefore essential to achieve a stable and long-lasting remission., Methods: Melatonin actions were analysed by viability cell assays, flow cytometry, quantitative PCR for mRNA expression, western blot for protein expression and quantitative and qualitative promoter methylation methods., Results: Combinations of melatonin and chemotherapeutic drugs (including temozolomide, current treatment for malignant gliomas) have a synergistic toxic effect on BTSCs and A172 malignant glioma cells. This effect is correlated with a downregulation of the expression and function of the ABC transporter ABCG2/BCRP. Melatonin increased the methylation levels of the ABCG2/BCRP promoter and the effects on ABCG2/BCRP expression and function were prevented by preincubation with a DNA methyltransferase inhibitor., Conclusion: Our results point out a possible relationship between the downregulation of ABCG2/BCRP function and the synergistic toxic effect of melatonin and chemotherapeutic drugs. Melatonin could be a promising candidate to overcome multidrug resistance in the treatment of glioblastomas, and thus improve the efficiency of current therapies.

INTRODUCTION. Brain cavernoma are a type of arteriovenous malformation that clinically presenting seizures, neurological deficit or bleeding. Hypoxia, neoangiogenesis and metalloproteasas seems to be involved in seizures physiopathology. Our study aims to assess this potential relation by immunohistochemical methods, analyzing hypoxia inducible factor (HIF-1alpha) and metalloproteasa (MMP-9) in tissue surrounding cavernoma. PATIENTS AND METHODS. We selected 17 consecutive cases anatomopathologically diagnosed as cavernoma during 9 years. Immunohistochemical staining was performed for HIF-1alpha and MMP-9. We evaluated the relation between seizures and the scale of uptake of different tissues surrounding cavernoma. RESULTS. Cases with seizures had HIF-1alpha positive uptake in vascular endothelium in 31%, 17% in fibrous tissue and 34% in inflammatory tissue. Besides, it also shows MMP-9 positive uptake in vascular endothelium in 86%, 100% in fibrous tissue and 43% of brain tissue. Statistical analysis by chi-square and odds ratio shows a positive trend towards seizures and the presence of HIF-1alpha and MMP-9 in vascular tissue, fibrous tissue and brain tissue, but no for inflammatory tissue. CONCLUSION. HIF-1alpha and MMP-9, valued by immunohistochemical methods, are related to complications as seizures.

Rosai-Dorfman disease is a rare, benign, idiopathic histio-proliferative disorder. Only 5% of cases involve the central nervous system. We describe a 10-year-old girl with pain in her lower limbs and back. Spinal magnetic resonance imaging revealed an intradural extramedullary lesion at T9-T10. We decided on surgical treatment. An anatomic/pathologic examination revealed histiocytic-like cells and extensive fibrosis. Immunohistochemistry revealed positivity for CD68 protein and negativity for CD1a protein. Craniospinal magnetic resonance imaging demonstrated an extra-axial lesion in the right frontal region, a small nodule in the left middle cerebellar peduncle, and another small lesion in the right ventral pons. We performed a complete removal of the frontal lesion. The histologic examination produced results compatible with Rosai-Dorfman disease. Most lesions in intracranial Rosai-Dorfman disease mimic meningioma. The definitive diagnosis relies on pathologic and immunohistochemical characteristics. Surgical removal is generally regarded as the treatment of choice. Disease progression after surgical resection is uncommon. Surgical treatment is not recommended until clear disease progression is detected, or focal disease causes neurologic compression. This disease must be included in the differential diagnosis of lesions that mimic meningioma., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Cluster headache is included in the group of trigeminal autonomic cephalalgias. Although the pathophysiology of cluster headache has not yet been sufficiently established, the theory of a central origin tells us that this headache is produced by hypothalamic dysfunction. More than 50 patients have been treated with deep brain stimulation of the posterior nucleus of the hypothalamus from 2001. The results show clinical improvement in more than 60% of the cases, opening a promising issue for the treatment of the cluster headache persistent after medical treatment. The surgical target that have been used until now is based on the origin of the cluster headache in the hypothalamic dysfunction. Nevertheless, It has still some open questions as the lack of proving the posterior nucleus of the hypothalamus is the real origin of the cluster headache, the lack of consensus about the anatomy of the surgical target and the variability of the structures stimulated with the surgery. The aim of this article is a review of the target used and propose another surgical target based on physiopathological concepts to explain the improvement with the deep brain stimulation in these patients.

The purpose was to determine the incidence of lead fracture in patients with DBS over a long period of time. We present a retrospective study of 208 patients who received 387 DBS electrodes. Fourteen patients had sixteen lead fractures (4% of the implanted leads) and two patients suffered from 2 lead fractures. Of all lead fractures, five patients had the connection between the leads and the extension cables located in mastoids region, ten in cervical area and one in thoracic region. The mean distance from the connection between the electrode and the extension cable and the lead fracture was 10.7 mm. The lead fracture is a common, although long-term complication in DBS surgery. In our experience, the most common site of electrode cable breakage is approximately between 9 and 13 mm from the junction between the lead and the extension cable. The most important cause of lead fracture is the rotational movement of the lead-extension cable system. If we suspect lead fracture, we must check the impedance of the electrode and to evaluate the side effects of voltage. Finally, we must conduct a radiological screening.

Introduction: Decompressive craniectomy increases the survival rate in cases of malignant middle cerebral artery (MCA) stroke. The imaging and clinical signs that predict a malignant progression of stroke of the MCA are analysed, together with factors associated with a poorer prognosis., Patients and Methods: The study involved 30 patients, who were divided into three groups: patients who had undergone surgery, and patients who had not undergone surgery but were admitted to intensive care or to neurology wards. The surgical procedure consisted in creating a bone window with a diameter of at least 10 cm and a dural opening. The initial evaluation of the patient was performed using the Glasgow scale and the National Institute of Health stroke scale; follow-up was carried out using the modified Rankin scale, the Barthel index and the Glasgow Outcome Scale at six months., Results: Younger patients have a better functional prognosis than those over 60 years of age. A deviation of more than 10 mm from the mean line is associated with a poorer prognosis, as are volumes of infarcted tissue above 350 cm3. Lower scores on the Glasgow scale on admission are associated with a poorer prognosis for survival and a higher number of sequelae, as well as their reduction during hospitalisation., Conclusions: Age conditions the presence of sequelae in these patients. The presence of clinical signs of herniation (anisocoria, lower initial score or important drop on the Glasgow scale) and imaging signs (displacement of the mean line, volume of infarcted tissue) imply a poorer prognosis. Early surgery in those patients in whom it is indicated reduces the number of sequelae and increases the rate of survival.

Objectives: We report our experience and results with extradural cortical stimulation (ECS) in the surgical treatment of Parkinson's Disease (PD). Besides, we review the literature supporting the use of this technique., Materials and Methods: Six patients with advanced PD and exclusion criteria for Deep Brain Stimulation (DBS) were included in our ECS protocol. With the aid of functional MRI and somato-sensory evoked potentials monitoring, the motor cortex projection over the scalp was drawn. Finally, under local anesthesia a stimulation lead was placed in the epidural space overlying the central sulcus., Results: Patients showed mild daily life activities improvement with a slightly lower levodopa equivalent dose, but UPDRS part III scores showed no significant modification., Conclusions: Despite ECS is a minimally invasive surgical technique, our results only support its use in selected patients with advanced PD, in whom this therapy may be modestly effective. More experimental studies regarding the neuromodulation of the basal ganglia-cortex loops are required to optimize its clinical application.

Introduction: The obsessive-compulsive disorder (OCD) has an incidence in general population of 1.5-3%. If we consider as a positive respond a diminution of the 25-35% in the symptoms of OCD according to the Y-BOCS, and we add the cognitive-behavioral therapy to the pharmacological treatment, only a 40-60% of treated patients would have significant improvement and a 10% of patients with OCD, would be refractory to all type of medical treatment., Development: Current neurosurgical techniques for resistant cases of OCD interrupt the connections between the frontal lobes and subcortical structures (cingulotomy, capsulotomy). These techniques are ablative and irreversible. It shows the importance of finding a less aggressive technique with better clinical results. Deep brain stimulation (DBS) is an alternative to traditional neurosurgery based in neuromodulation methods. It's considered that the physiopathology of the OCD consists of a dysfunction of the direct and indirect vias that control the extrapiramidal limbic circuit. On the other hand, it had been obtained positive results after DBS of the subthalamic nucleus of three patients with Parkinson's disease and OCD., Conclusion: This article has as target the demonstration that bilateral DBS of the limbic part of the subthalamic nucleus is an alternative for the treatment of refractory OCD.

Background: Deep brain stimulation (DBS) is a surgical technique used to alleviate symptoms in patients with advanced Parkinson's disease (PD). It is a reversible procedure and its effect is based on electrical modulation of the nervous system and has considerable advantages in morbidity-mortality when compared to lesion techniques such as thalamotomy and/or pallidotomy. The objective was to evaluate the adverse events during the surgical placement of leads in the subthalamic nucleus for the treatment of Parkinson's disease., Methods: A retrospective data collection was made in a total of 130 patients in whom we performed 272 procedures for the implant of leads in the subthalamic nucleus between May 1998 and December 2005. All the patients were operated by the same surgeon, in the same institution and with the same surgical methodology. The complications under evaluation were: aborted procedure, misplaced leads, intracranial haemorrhage, seizures, hardware complications and other complications., Results: 130 patients were treated (62 women, 68 men; average age 62 (36-74) years). The average duration of disease from the time of diagnosis to operation was 15.3 years (4-28 years) and the mean follow-up was of 37 months (3-93 months). One hundred and twenty four patients were implanted bilaterally and 6 unilaterally. 62% did not present any complications, 30% had one complication, and 8% more than one complication. Aborted procedures amounted to 5.14% of all procedures, misplaced leads 2.2%, intracranial haemorrhage 3.3%, seizures 4.7%, hardware complications 1.8% and other complications 5.1%., Conclusion: Deep brain stimulation surgery is an effective and safe method to treat Parkinson's disease with a low incidence of permanent adverse events.