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Background and importance Deep brain stimulation of the posteromedial hypothalamus (PMH DBS) appears to be an effective treatment for drug-resistant aggressiveness. Weaver syndrome (WS) is a rare genetic disorder in which patients develop some degree of intellectual disability and rarely severe behavioral alterations that may benefit from this procedure. Clinical presentation We present the case of a 26-yr-old man diagnosed with WS presenting with uncontrollable self and heteroaggressiveness and disruptive behavior refractory to pharmacological treatment and under severe physical and mechanical restraining measures. The patient was successfully treated with bilateral PMH DBS resulting in affective improvement, greater tolerance for signs of affection, regularization in his sleep pattern and appetite disturbances at 12-mo follow-up. A detailed description and video of the procedure are presented, and a review of the clinical characteristics of WS and the utility and benefits of PMH DBS for refractory aggressiveness are reviewed. Conclusion To our knowledge, this is the first case of refractory aggressiveness described in WS as well as the first patient with WS successfully treated with PMH DBS.

OBJECTIVEInitial studies applying deep brain stimulation (DBS) of the posteromedial hypothalamus (PMH) to patients with pathological aggressiveness have yielded encouraging results. However, the anatomical structures involved in its therapeutic effect have not been precisely identified. The authors’ objective was to describe the long-term outcome in their 7-patient series, and the tractography analysis of the volumes of tissue activated in 2 of the responders.METHODSThis was a retrospective study of 7 subjects with pathological aggressiveness. The findings on MRI with diffusion tensor imaging (DTI) in 2 of the responders were analyzed. The authors generated volumes of tissue activated according to the parameters used, and selected those volumes as regions of interest to delineate the tracts affected by stimulation.RESULTSThe series consisted of 5 men and 2 women. Of the 7 patients, 5 significantly improved with stimulation. The PMH, ventral tegmental area, dorsal longitudinal fasciculus, and medial forebrain bundle seem to be involved in the stimulation field.CONCLUSIONSIn this series, 5 of 7 medication-resistant patients with severe aggressiveness who were treated with bilateral PMH DBS showed a significant long-lasting improvement. The PMH, ventral tegmental area, dorsal longitudinal fasciculus, and medial forebrain bundle seem to be in the stimulation field and might be responsible for the therapeutic effect of DBS.

Background and Objective Learning a new technique in neurosurgery is a big challenge especially for trainees. In recent years, simulations and simulators got into the focus as a teaching tool. Our objective is to propose a simulator for placement of cortical bone trajectory (CBT) screws to improve results and reduce complications.Methods We have created a platform consisting of a sawbone navigated with a 3D fluoroscope to familiarize our trainees and consultants with CBT technique and later implement it in our department. Objective Structured Assessment of Technical Skills (OSATS) and Physician Performance Diagnostic Inventory Scale (PPDI) were obtained before and after the use of the simulator by the five participants in the study. Patients who were operated on after the implementation of the technique were retrospectively reviewed.Results During the simulation, there were 4 cases of pedicle breach out of 24 screws inserted (16.6%). After having completed simulation, participants demonstrated an improvement in OSATS and PPDI (p = 0.039 and 0.042, respectively). Analyzing the answers to the different items of the tests, participants mainly improved in the knowledge (p = 0.038), the performance (p = 0.041), and understanding of the procedure (p = 0.034). In our retrospective series, eight patients with L4–L5 instability were operated on using CBT, improving their Oswestry Disability Index (ODI) score (preoperative ODI 58.5 [SD 16.7] vs. postoperative ODI 31 [SD 13.4]; p = 0.028). One intraoperative complication due to a dural tear was observed. In the follow-up, we found a case of pseudoarthrosis and a facet joint violation, but no other complications related to misplacement, pedicle fracture, or hardware failure.Conclusion The simulation we have created is useful for the implementation of CBT. In our study, consultants and trainees have valued very positively the learning obtained using the system. Moreover, simulation facilitated the learning of the technique and the understanding of surgical anatomy. We hope that simulation helps reducing complications in the future.

INTRODUCTION We analysed the decompression obtained by dorsal or dorsolumbar corpectomy measured by Cobb angle and the spinal area prior to and after surgery and compared the evolution of the technique over the last five years of the study. MATERIAL AND METHOD A retrospective review of patients operated between 2005 and 2015 through anterior or posterior approaches was performed. RESULTS 24 patients were studied and a significant improvement was observed between the preoperative and postoperative morphometrical measurement (4.18° correction of the kyphosis and an increase of 130.8mm2 in the spinal canal, p

Resumen Introduccion Hemos analizado la descompresion obtenida mediante corpectomia dorsal o dorsolumbar medida a traves del angulo de Cobb y el area del canal medular antes y despues de la cirugia. Ademas, se ha comparado la evolucion de la tecnica entre los primeros 5 anos del estudio y los 5 posteriores. Material y metodo Se realizo un estudio retrospectivo de los pacientes operados entre 2005-2015 en nuestro centro mediante abordajes anteriores y posteriores. Resultados Se intervinieron 24 pacientes y observamos una mejoria significativa entre los valores preoperatorios y postoperatorios en el analisis morfometrico (correccion de 4,18° de cifosis y un aumento del area del canal medular de 130,8 mm2 con una significacion de p Conclusiones La corpectomia dorsal permite una descompresion espinal significativa, con mejoria de la funcion neurologica sin que se correlacione con las mediciones de la descompresion. Gracias a las mejoras tecnicas, las tecnicas minimamente invasivas (abordajes posteriores y tecnicas MISS) permiten unos buenos resultados funcionales que son similares a los obtenidos con tecnicas anteriores.

ObjectivesThe large number of infected patients requiring mechanical ventilation has led to the postponement of scheduled neurosurgical procedures during the first wave of the COVID-19 pandemic. The aims of this study were to investigate the factors that influence the decision to postpone scheduled neurosurgical procedures and to evaluate the effect of the restriction in scheduled surgery adopted to deal with the first outbreak of the COVID-19 pandemic in Spain on the outcome of patients awaiting surgery.DesignThis was an observational retrospective study.SettingsA tertiary-level multicentre study of neurosurgery activity between 1 March and 30 June 2020.ParticipantsA total of 680 patients awaiting any scheduled neurosurgical procedure were enrolled. 470 patients (69.1%) were awaiting surgery because of spine degenerative disease, 86 patients (12.6%) due to functional disorders, 58 patients (8.5%) due to brain or spine tumours, 25 patients (3.7%) due to cerebrospinal fluid (CSF) disorders and 17 patients (2.5%) due to cerebrovascular disease.Primary and secondary outcome measuresThe primary outcome was mortality due to any reason and any deterioration of the specific neurosurgical condition. Second, we analysed the rate of confirmed SARS-CoV-2 infection.ResultsMore than one-quarter of patients experienced clinical or radiological deterioration. The rate of worsening was higher among patients with functional (39.5%) or CSF disorders (40%). Two patients died (0.4%) during the waiting period, both because of a concurrent disease. We performed a multivariate logistic regression analysis to determine independent covariates associated with maintaining the surgical indication. We found that community SARS-CoV-2 incidence (OR=1.011, pConclusionsPatients awaiting neurosurgery experienced significant collateral damage even when they were considered for scheduled procedures.

Objective High grade spondylolisthesis (HGS) is a quite rare entity and many techniques are available to address this condition. In 1994 Abdu et al. proposed a transdiscal fixation approach that achieved a good clinical outcome. We analyse outcome and fusion achieved in patients treated by transdiscal fixation after 1-year follow-up. Methods We reviewed patients operated through transdiscal fixation since 2014 with a follow-up of at least 1 year, and compared preoperative and postoperative clinical measures (ODI, VAS and EQ-5D) and postoperative complications. Also, we analyzed the degree of fusion on CT scan with Lenke and Birdwell criteria. Results Twelve patients were included in the study with a mean follow-up of 49.4 months (range 12.8–84.1 months). Three cases presented a Meyerding grade IV spondylolisthesis and 9 cases grade III. At 1-year follow-up mean postoperative ODI, VAS and EQ5D scores improved (ODI 13.2 (range 0–30) vs 49.83 (range 15–71.1); p = .005). Equally this improvement was seen in the last follow-up (ODI 9.28 (range 0–35) vs 49.83 (range 15–71.1); p = .005). CT scan showed fusion grade A in 5 patients (41.6%), another 5 as grade B (41.6%) in Lenke classification. According to the Birdwell criteria 4 patients were classified as grade I (33.3%), 7 patients grade II (58.3%). None showed complications postoperatively or radiolucency in follow-up. Conclusions Transdiscal fixation shows a good clinical outcome that is maintained throughout a long time period and provides a reliable and suitable fusion.

ObjectiveTo assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain.SettingsThe initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied.ParticipantsThis was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020.InterventionsAn exploratory factorial analysis was performed to select the most relevant variables of the sample.Primary and secondary outcome measuresUnivariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection.ResultsSixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/105people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade ≥3 (OR 2.5) and preoperative GCS 3–8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test 5people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated.ConclusionsPerioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/105people/week) was a statistically independent predictor of mortality.Trial registration numberCEIM 20/217.

OBJECTIVE Language lateralization is a major concern in some patients with pharmacoresistant epilepsy who will face surgery; in these patients, hemispheric dominance testing is essential to avoid further complications. The Wada test is considered the gold standard examination for language localization, but is invasive and requires many human and material resources. Functional MRI and tractography with diffusion tensor imaging (DTI) have demonstrated that they could be useful for locating language in epilepsy surgery, but there is no evidence of the correlation between the Wada test and DTI MRI in language dominance. METHODS The authors performed a retrospective review of patients who underwent a Wada test before epilepsy surgery at their institution from 2012 to 2017. The authors retrospectively analyzed fractional anisotropy (FA), number and length of fibers, and volume of the arcuate fasciculus and uncinate fasciculus, comparing dominant and nondominant hemispheres. RESULTS Ten patients with temporal lobe epilepsy were reviewed. Statistical analysis showed that the mean FA of the arcuate fasciculus in the dominant hemisphere was higher than in the nondominant hemisphere (0.369 vs 0.329, p = 0.049). Also, the number of fibers in the arcuate fasciculus was greater in the dominant hemisphere (881.5 vs 305.4, p = 0.003). However, no differences were found in the FA of the uncinate fasciculus or number of fibers between hemispheres. The length of fibers of the uncinate fasciculus was longer in the dominant side (74.4 vs 50.1 mm, p = 0.05). Volume in both bundles was more prominent in the dominant hemisphere (12.12 vs 6.48 cm3, p = 0.004, in the arcuate fasciculus, and 8.41 vs 4.16 cm3, p = 0.018, in the uncinate fasciculus). Finally, these parameters were compared in patients in whom the seizure focus was situated in the dominant hemisphere: FA (0.37 vs 0.30, p = 0.05), number of fibers (114.4 vs 315.6, p = 0.014), and volume (12.58 vs 5.88 cm3, p = 0.035) in the arcuate fasciculus were found to be statistically significantly higher in the dominant hemispheres. Linear discriminant analysis of FA, number of fibers, and volume of the arcuate fasciculus showed a correct discrimination in 80% of patients (p = 0.024). CONCLUSIONS The analysis of the arcuate fasciculus and other tract bundles by DTI could be a useful tool for language location testing in the preoperative study of patients with refractory epilepsy.

An integrated pulsed laser driver in a 0.18- $\mu \text{m}$ CMOS technology has been developed for generating configurable and stable laser diode pulses for time-of-flight applications. The duration of the output optical laser pulses can be configured from below 100 ps up to 5 ns, with 1-ps typical resolution, by a combination of a coarse and a fine delay generator. The pulse-width stability has been designed against process, supply voltage and temperature variations. This has been carried out using a system with two phase-locked loops that regulate the supply voltage of the chain of inverters, found in the driver and pre-driver improving by 2.5 times the stability compared to the case, where a fixed supply voltage is applied. Laser current can be configured up to 500 mA and output pulses are generated at a repetition rate up to 200 MHz.

Finding effective treatment options for patients with brain metastasis remains an unmet need. Given the limitations imposed by the blood-brain-barrier for systemic approaches, radiotherapy offers a superior ability to access the brain. While clinical practice recently adapted the use of stereotactic radiosurgery (SRS), Whole-Brain-Radiotherapy (WBRT) continuous to be an important treatment option, since many patients present with multifocal lesions or bad performance scores, rendering them ineligible for SRS. Unfortunately, overall survival of patients remains unaffected by radiotherapy. Despite this clinical data, the molecular mechanisms that allow metastatic cells to resist radiotherapy in the brain is unknown. We have applied WBRT to experimental brain metastasis from lung and breast adenocarcinoma and validated their resistance in vivo. An unbiased search to identify potential mediators of resistance identified the S100A9-RAGE-NFkB-JunB pathway. Targeting this pathway genetically reverts the resistance to radiotherapy and increases therapeutic benefits in vivo. In two independent cohorts of brain metastasis from lung and breast adenocarcinoma patients, levels of S100A9 correlate with the response to radiotherapy, offering a novel approach to stratify patients according to their expected benefit. In order to make this biomarker also available for brain metastasis patients receiving palliative WBRT without preceding surgery, we complemented our tumor-specimen based approach with the less invasive detection of S100A9 from liquid biopsies. Here, serum S100A9 also correlated with a worse response to WBRT in brain metastasis patients. Furthermore, we have validated the use of a blood-brain-barrier permeable RAGE inhibitor to restore radio-sensitivity in experimental brain metastasis models in vivo and in patient-derived organotypic cultures of radio-resistant brain metastasis ex vivo. In conclusion, we identified S100A9 as a major mediator of radio-resistance in brain metastasis and offer the molecular framework to personalize radiotherapy by exploiting it as a biomarker and as a therapeutic target, thus maximizing the benefits for the patient.

Background Glioblastoma is the most frequent primary brain tumor and despite of complete treatment survival is still poor. The aim of this study is to define the utility of reoperation for improving survival in patients with recurrent glioblastoma, and determine other prognostic factors associated with longer survival. Methods We performed a retrospective analysis of those patients who underwent surgery and compared those who were operated two or more times and those who received surgery only once. We studied overall survival (OS), progression-free survival (PFS), and clinical variables that could be related with higher survival. Results A total of 121 patients were eligible for the study, of whom 31 (25%) underwent reoperation. The reoperation group had a mean and median increase survival of 10.5 and 16.4 months in OS and 3.5 and 2.7 months for PFS compared with the non-reoperation group ( P 2 = 1.86; P = 0.40). Cox multivariable analysis revealed that age (hazard ratio [HR] 1.03; 95% confidence interval [CI], 1.006–1.055; P = 0.013), reoperation (HR, 0.48; 95% CI, 0.285–0.810; P = 0.006), extent of resection >95% (HR, 0.547; 95% CI, 0.401–0.748; P P = 0.003) were correlated with a higher OS. Conclusions Reoperation and the extent of resection (EOR) are the only surgical variables that neurosurgeons can modify to improve survival in our patients. Higher EOR and reoperation rates in patients who can be candidates for second surgery, will increase OS and PFS.

This article summarizes recent evidence on the cortical bone trajectory (CBT) obtained from published anatomical, biomechanical, and clinical studies. CBT was proposed by Santoni in 2009 as a new trajectory that can improve the fixation of pedicle screws in response to screw loosening in osteoporotic patients. Recently, research interest has been growing with increasing numbers of published series and frequent reports of new applications. We performed an online database search using the terms “cortical bone trajectory,” “pedicle screw,” “CBT spine,” “CBT fixation,” “MISS CBT,” and “traditional trajectory.” The search included the PubMed, Ovid MEDLINE, Cochrane, and Google Scholar databases, resulting in an analysis of 42 articles in total. These covered three aspects of CBT research: anatomical studies, biomechanical parameters, and clinical cases or series. Compared to the traditional trajectory, CBT improves pullout strength, provides greater stiffness in cephalocaudal and mediolateral loading, and shows superior resistance to flexion/extension; however, it is inferior in lateral bending and axial rotation. CBT seems to provide better immediate implant stability. In clinical studies, CBT has shown better perioperative results for blood loss, length of stay in hospital, and surgery time; similar or better clinical postoperative scores; and similar comorbidity, without any major fixation system complications due to instrumentation failure or screw misplacement. In addition, advantages such as less lateral exposure allow it to be used as a minimally invasive technique. However, most of the clinical studies were retrospective case series or case-control studies; prospective evidence on this technique is scarce, making a definitive comparison with the traditional trajectory difficult. Nevertheless, we can conclude that CBT is a safe technique that offers good clinical results with similar biomechanical and perioperative parameters to those of the traditional trajectory. In addition, new applications can improve its results and make it useful for additional pathologies.

Glioblastoma (GBM) is the most frequent intraaxial malignant brain tumour, in which recurrence management is a frequent and demanding issue. Recently, reintervention has emerged as a useful tool for treatment. However, some new evidence has shown that most of the articles published could have overestimated its effects. We aimed to analyse the effect on survival of reintervention considering it as a time-dependent variable and to compare it with classic statistical analysis. We performed a retrospective study with GBM patients between 2007 and 2017. We compared the overall survival (OS) between reintervention and non-reintervention groups with time-dependent statistical methods (Simon-Makuch and landmarking methods and time-dependent multivariable Cox analysis) and compared them with those obtained with non-dependent time variable analysis. A total of 183 patients were included in the analysis and 44 of them were reoperated. The standard analysis with Kaplan-Meier and multivariable Cox regression of the cohort showed an OS of 22.2 months (95% CI 12.56–16.06) in the reintervention group and 11.8 months (95% CI 9.87–13.67) in the non-reintervention group (p

Background Meningiomas arising at the pineal region are a rare entity and still represent a great neurosurgical challenge given their deep location and critical neuroanatomic relationships. The optimal surgical approach to treat these lesions is still under debate. Our objective is to review the topographic and diagnostic features of these lesions, which can help to guide an optimal surgical outcome. Methods We present 2 clinical cases of falcotentorial meningiomas successfully treated at our institution (2016–2017) with different surgical approaches. A literature review is performed, and a description of the classification, anatomic relationships, clinical features, diagnosis, and different surgical options and outcomes of these lesions is presented. Results The first patient was treated via a supracerebellar infratentorial approach, and the second patient was treated via a parieto-occipital interhemispheric approach. In both tumors, a gross total resection was achieved with no permanent neurologic deficits. In the literature review, gross total resection rates range from 33% to 100%, with no differences regarding the type of meningioma or the surgical approach performed. Permanent neurologic morbidity varies from 0% to 50%, and mortality rates range from 0% to 23%. The distortion and displacement of the vein of Galen and straight sinus represent the most important feature in the decision of optimal surgical approach. Conclusions Pineal region meningiomas represent very infrequent, challenging lesions, and their description in the literature is scarce. The systematic topographic classification of these tumors and evaluation of the neuroanatomic structures involved are crucial to guide a safe and optimal surgical approach and achieve satisfactory outcomes.

OBJECTIVESpondylolisthesis is a prevalent spine disease that recent studies estimate could be detected in 9% of the population. High-grade spondylolisthesis (HGS), however, is much less frequent, which makes it difficult to develop a general recommendation for its treatment. Posterior transdiscal fixation was proposed in 1994 for HGS, and the use of spine navigation could make this technique more accessible and reduce the morbidity associated with the procedure. The purpose of this study was to present a case series involving adult patients with HGS and correct spinal alignment who were treated with transdiscal pedicle screw placement guided with neuronavigation and compare the results to those achieved previously without image guidance.METHODSThe authors reviewed all cases in which adult patients with correct spinal alignment were treated for HGS with posterior transdiscal instrumentation placement guided with navigation between 2014 and 2016 at their institution. The authors compared preoperative and postoperative spinopelvic parameters on standing radiographs as well as Oswestry Disability Index (ODI) scores and visual analog scale (VAS) scores for low-back pain. Follow-up CT and MRI studies and postoperative radiographs were evaluated to identify any screw malplacement or instrumentation failure. Any other intraoperative or postoperative complications were also recorded.RESULTSEight patients underwent posterior transdiscal navigated instrumentation placement during this period, with a mean duration of follow-up of 16 months (range 9–24 months). Six of the patients presented with Meyerding grade III spondylolisthesis and 2 with Meyerding grade IV. In 5 cases, L4–S1 instrumentation was placed, while in the other 3 cases, surgery consisted of transdiscal L5–S1 fixation. There was no significant difference between preoperative and postoperative spinopelvic parameters. However, there was a statistically significant improvement in the mean VAS score for low-back pain (6.5 ± 1.5 vs 4 ± 1.7) and the mean ODI score (49.2 ± 19.4 vs 37.7 ± 22) (p = 0.01 and p = 0.012, respectively). Six patients reduced their use of pain medication. There were no intraoperative or postoperative complications during the hospital stay, and as of the most recent follow-up, no complications related to pseudarthrosis or hardware failure had been observed.CONCLUSIONSTreatment with posterior transdiscal pedicle screws with in situ fusion achieved good clinical and radiological outcomes in patients with HGS and good sagittal spinal balance. The use of navigation and image guidance was associated with improved results in this technique, including a reduction in postoperative and intraoperative complications related to screw malplacement, pseudarthrosis, and instrumentation failure.