Refining Stereotaxic Neurosurgery Techniques and Welfare Assessment for Long-Term Intracerebroventricular Device Implantation in Rodents.

Stereotaxic surgeries enable precise access to specific brain regions, being of particular interest for chronic intracerebroventricular drug delivery. However, the challenge of long-term studies at this level is to allow the implantation of drug storage devices and their correct intrathecal connection while guaranteeing animal welfare during the entire study period. In this study, we propose an optimized method for safe intrathecal device implantation, focusing on preoperative, intraoperative, and postoperative procedures, following the 3Rs principle and animal welfare regulations. Our optimized protocol introduces three main refinements. Firstly, we modify the dimensions of the implantable devices, notably diminishing the device-to-mouse weight ratio. Secondly, we use a combination of cyanoacrylate tissue adhesive and UV light-curing resin, which decreases surgery time, improves healing, and notably minimizes cannula detachment or adverse effects. Thirdly, we develop a customized welfare assessment scoresheet to accurately monitor animal well-being during long-term implantations. Taken together, these refinements positively impacted animal welfare by minimizing the negative effects on body weight, surgery-related complications, and anxiety-like behaviors. Overall, the proposed refinements have the potential to reduce animal use, enhance experimental data quality, and improve reproducibility. Additionally, these improvements can be extended to other neurosurgical techniques, thereby advancing neuroscience research, and benefiting the scientific community.

Risk Factors Associated With Inadequate Brain Relaxation in Craniotomy for Surgery of Supratentorial Tumors.

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, PaCO2, 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.

Evaluation of Titanium Serum Levels in Patients After Spine Instrumentation: Comparison Between Posterolateral and 360º Spinal Fusion Surgery.

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.

Long-Term Results of Deep Brain Stimulation of the Mamillotegmental Fasciculus in Chronic Cluster Headache.

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.

Meningioma Associated with Brain Aneurysm: Report of Two Cases.

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.

Prognostic factors and survival study in high-grade glioma in the elderly.

Background Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumour in adults. Due to the ageing of the population, diagnosis in the elderly is becoming more common. The aim of this study was to analyse different combinations of treatments and to identify preoperative factors, including O6-methylguanine-DNA methyltransferase status, that may be associated with decreased survival among patients older than 70 years. Methods and materials We retrospectively included all patients over 70 years of age, who underwent surgery at the Department of Neurosurgery (HUCA and HUMV) and were diagnosed of GBM by pathological criteria from January 2007 to September 2014. Results Eighty-one patients were analysed, whose mean age was 75 (SD 4) and 48 were male. Karnofsky performance status (KPS) was over 70 in 61 patients and 38.3% presented with motor deficit. Sixty-three patients underwent resection, and 18 had only a diagnostic biopsy. The complication rate was 17.28% and mortality rate was 7.4%. Survival was increased in patients who received radiotherapy (n = 41) or additional chemotherapy (n = 26) (p < 0.001). KPS < 70 was an independent factor associated with low-rate survival. Patients with optimal treatment had a median survival of 8 months compared to patients with suboptimal treatment who had a median survival of 4 months (p < 0.001). Conclusions This study suggests that KPS is the most important preoperative prognostic factor. Maximal safe resection followed by radical radiotherapy and temozolomide might be the optimal treatment of choice since glioblastoma-diagnosed patients over 70 years of age showed a statistically significant survival benefit.

Involvement of autophagy in melatonin-induced cytotoxicity in glioma-initiating cells.

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.

Surgical adverse events of deep brain stimulation in the subthalamic nucleus of patients with Parkinson's disease. The learning curve and the pitfalls.

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.

Calidad de vida tras el tratamiento quirúrgico del infarto maligno de la arteria cerebral media / Quality of life following surgical treatment of malignant middle cerebral artery infarction

Introducción. Son escasas las publicaciones que valoran la capacidad de adaptación a la enfermedad de pacientes con infarto maligno de la arteria cerebral media sometidos a cirugía descompresiva. El propósito del trabajo es analizar la calidad de vida final y el grado de satisfacción de pacientes y familiares. Pacientes y métodos. Analizamos 21 pacientes al año de ser intervenidos. Para evaluar la calidad de vida, empleamos la versión española del Sickness Impact Profile. Para conocer el grado de satisfacción retrospectiva, preguntamos a familiares y pacientes si, conociendo las secuelas actuales del afectado, habrían estado igualmente de acuerdo con realizar la craniectomía descompresiva. Resultados. La esfera física se percibe como más perturbada que la relativa a aspectos emocionales. No existen diferencias en la calidad de vida entre pacientes con afectación del hemisferio derecho o izquierdo. Los pacientes con mejor situación funcional refieren una mejor calidad de vida. El 81% de los pacientes se encuentra satisfecho. Conclusión. A pesar de que todos los pacientes muestran una reducción en la calidad de vida después de la craniectomía descompresiva, la mayoría parecen satisfechos con el tratamiento recibido, incluso en afectación del hemisferio dominante o aquéllos con una discapacidad moderada-grave (AU)

Introduction. Little work has been published on the capacity to adapt to the disease of patients with malignant middle cerebral artery infarction who have undergone decompressive surgery. The purpose of this study is to analyse the final quality of life and the degree of satisfaction of patients and their relatives. Patients and methods. We analysed 21 patients one year after their operation. The quality of life was evaluated using the Spanish version of the Sickness Impact Profile. In order to determine the degree of retrospective satisfaction, we asked relatives and patients whether, now that the patient’s current sequelae are known, they would have still agreed to a decompressive craniectomy. Results. The physical sphere is felt to be more disrupted than that concerning emotional aspects. There are no differences in the quality of life between patients who have the right or the left hemisphere affected. Patients with a better functional situation report a better quality of life. Altogether, 81% of patients said they were satisfied. Conclusions. Despite the fact that all the patients show a loss of quality of life after a decompressive craniectomy, most of them seem to be satisfied with the treatment they have received, even in cases in which the dominant hemisphere is compromised or in those with a moderate-severe disability (AU)

[Quality of life following surgical treatment of malignant middle cerebral artery infarction]. / Calidad de vida tras el tratamiento quirúrgico del infarto maligno de la arteria cerebral media.

INTRODUCTION: Little work has been published on the capacity to adapt to the disease of patients with malignant middle cerebral artery infarction who have undergone decompressive surgery. The purpose of this study is to analyse the final quality of life and the degree of satisfaction of patients and their relatives. PATIENTS AND METHODS: We analysed 21 patients one year after their operation. The quality of life was evaluated using the Spanish version of the Sickness Impact Profile. In order to determine the degree of retrospective satisfaction, we asked relatives and patients whether, now that the patient's current sequelae are known, they would have still agreed to a decompressive craniectomy. RESULTS: The physical sphere is felt to be more disrupted than that concerning emotional aspects. There are no differences in the quality of life between patients who have the right or the left hemisphere affected. Patients with a better functional situation report a better quality of life. Altogether, 81% of patients said they were satisfied. CONCLUSIONS: Despite the fact that all the patients show a loss of quality of life after a decompressive craniectomy, most of them seem to be satisfied with the treatment they have received, even in cases in which the dominant hemisphere is compromised or in those with a moderate-severe disability.

Multiple involvement of the central nervous system in Rosai-Dorfman disease.

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.

Lead Fractures in Deep Brain Stimulation during Long-Term Follow-Up.

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.