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Background: The epidermal growth factor receptor (EGFR) regulates important cellular processes and is frequently implicated in human tumors. Three EGFR polymorphisms have been described as having a transcriptional regulatory function: two single-nucleotide polymorphisms in the essential promoter region, −216G/T and −191C/A, and a polymorphic (CA)n microsatellite sequence in intron 1. We aimed to elucidate the roles of these EGFR polymorphisms in glioma susceptibility and prognosis.Methods: We conducted a case–control study with 196 patients with glioma and 168 cancer-free controls. Unconditional multivariate logistic regression models were used to calculate ORs and 95% confidence intervals. A Cox regression model was used to evaluate associations with patient survival. False-positive report probabilities were also assessed.Results: None of the EGFR −216G/T variants was significantly associated with glioma risk. The −191C/A genotype was associated with higher risk for glioma when the (CA)n alleles were classified as short for ≤16 or ≤17 repeats. Independently of the (CA)n repeat cutoff point used, shorter (CA)n repeat variants were significantly associated with increased risk for glioma, particularly glioblastoma and oligodendroglioma. In all tested models with different (CA)n cutoff points, only −191C/A genotype was consistently associated with improved survival of patients with glioblastoma.Conclusions: Our findings implicate EGFR −191C/A and the (CA)n repeat polymorphisms as risk factors for gliomas, and suggest −191C/A as a prognostic marker in glioblastoma.Impact: Our data support a role of these EGFR polymorphisms in determining glioma susceptibility, with potential relevance for molecularly based stratification of patients with glioblastoma for individualized therapies. Cancer Epidemiol Biomarkers Prev; 20(12); 2610–7. ©2011 AACR.

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Most studies concerning intraoperative temporary arterial occlusion overlook the period between and after clip placement.To analyze the brain tissue oxygen tension through the process by which anterograde arterial blood flow is re-established after temporary clipping (TR).In this prospective observational study, patients who presented to surgery for middle cerebral artery aneurysms were continuously monitored with ICM+, to obtain temporal (downstream) PbtO2 levels while M1 segment temporary clips were applied and removed. PbtO2 changes were analyzed and compared with the clipping phase, and measures of exposure to hypoxia were defined and assessed during both phases and used in a model to test the impact of extending them.Eighty-six TRs (20 patients) were recorded. The mean acquired amount of time per clip release (CR) event was 336.7 seconds. Temporary clip removal produced specifically shaped, highly individual PbtO2 curves that correlated with their corresponding clipping phase events but developing slower and less consistently. The CR phase was responsible for greater cumulative exposure to hypoxia than the clip application phase through the first and second minutes of each. In our model, the duration of the TR phase was mostly responsible for the total exposure to hypoxia, and longer CR phases reduced the mean exposure to hypoxia.During the clip removal phase, the brain tissue is still exposed to oxygen levels that are significantly below the baseline, reverting through a singular, dynamic process. Therefore, it must be regarded by surgeons with the same degree of attention as its counterpart.

Diffuse astrocytoma (WHO grade II) has classically been considered a slow growing tumour, typically affecting young adults, with tendency for late malignant conversion. We describe a case of early atypical malignant transformation of diffuse astrocytoma seventeen months after complete surgical removal, as an intraventricular high-grade glioma (HGG). Retrospective laboratory findings for the presence of IDH 1/2 (isocitrate dehydrogenase) mutations were negative. There is growing evidence that IDH-wildtype (wt) astrocytomas behave more aggressively, therefore identifying IDH-mutation status should be mandatory in order to determine disease prognosis and guide treatment course. info:eu-repo/semantics/publishedVersion

Chronic neuropathic pain affects 7%-10% of the population. Deep brain stimulation (DBS) has shown variable but promising results in its treatment. This study prospectively assessed the long-term effectiveness of DBS in a series of patients with chronic neuropathic pain, correlating clinical results with neuroimaging. Sixteen patients received 5 years' post-surgical follow-up in a single center. Six had phantom limb pain after amputation and 10 had deafferentation pain after traumatic brachial plexus injury. Patient-reported outcome measures were completed before and after surgery, using VAS, UWNPS, BPI and SF-36 scores. Neuroimaging evaluated electrode location and effective volumes of activated tissue (VAT). Two subgroups were created based on the percentage of VAT superimposed upon the ventroposterolateral thalamic nucleus (eVAT), and clinical outcomes were compared. Analgesic effect was assessed at 5 years and compared to preoperative pain, with an improvement on VAS of 76.4% (p=0.0001), on UW-NPS of 35.2% (p=0.3582), on BPI of 65.1% (p=0.0505) and on SF-36 of 5% (p=0.7406). Eight patients with higher eVAT showed improvement on VAS of 67.5% (p=0.0017) while the remaining patients, with lower eVAT, improved by 50.6% (p=0.03607). DBS remained effective in improving chronic neuropathic pain after 5 years. While VPL-targeting contributes to success, analgesia is also obtained by stimulating surrounding posterior ventrobasal thalamic structures and related spinothalamocortical tracts.

Background Microsurgical clipping and endovascular coiling are viable treatment options for posterior communicating artery (PComA) aneurysms, but there are still major limitations to evidence-based decisions regarding standard-of-care treatment. In this study, we aimed at assessing potential selection biases that may influence our ability to extract conclusions about the comparative effectiveness or efficacy of the aneurysm treatment. Objective To study the patient/aneurysm characteristics as possible biases in the option for endovascular or neurosurgical treatment of PComA aneurysms. Methods A single-center, retrospective cohort study was performed, including all patients with treated PComA aneurysms with neurosurgical clipping or endovascular coiling between January 2010 and January 2021. Clinical and morphological data were collected from electronic records, and statistical analysis was performed. Results A total of 64 patients was eligible for inclusion; 24 (37.5%) patients were proposed for neurosurgical treatment, while 40 (62.5%) for endovascular treatment; 10 patients (25%) crossed over to the clipping group whereas none crossed over to the coiling side. Actual treatment analysis showed significantly higher diameters of mother vessel (t-test, p = 0.034) and aneurysm neck (Mann–Whitney, p = 0.029) in the clipping group and higher aspect and dome-to-neck ratios in the endovascular group (Mann–Whitney, p = 0.008). A significantly higher vasospasm frequency was found in the clipping group but only in the intention-to-treat analysis (Chi-square, p = 0.032). Conclusion Significant morphological differences between effective endovascular and surgical groups and differences in intention-to-treat analysis may limit the validity of a direct comparison between treatment options and suggest the presence of a possible selection bias.

Background Probabilistic brain mapping is a promising tool to estimate the expected benefit of pallidal deep brain stimulation (GPi‐DBS) in patients with isolated dystonia (IsoD). Objectives To investigate the role of probabilistic mapping in combined dystonia (ComD). Methods We rendered the pallidal atlas and the volume of tissue activated (VTA) for a cohort of patients with IsoD (n = 20) and ComD (n = 10) that underwent GPi‐DBS. The VTA was correlated with clinical improvement. Afterwards, each VTA was applied on the previously published probabilistic model (Reich et al., 2019). The correlation between predicted and observed clinical benefit was studied in a linear regression model. Results A good correlation between observed and predicted outcome was found for both patients with IsoD (n = 14) and ComD (n = 7) (r2 = 0.32; P

Objective Despite its widespread use, much is left to understand about the repercussions of parent artery temporary clipping in neurosurgery. This study seeks a better comprehension of the subject by aiming at the online measurement of brain tissue oxygen pressure (PbtO2) during such events. Methods This was a prospective observational study. Patients submitted to surgery for middle cerebral artery aneurysms (both ruptured and unruptured) were continuously monitored under Intensive Care Monitoring+ software, in order to obtain temporal (downstream) PbtO2 levels while temporary clips were applied. Separate PbtO2 curve events were identified, extracted, and processed. These were studied for assessing intraindividual and interindividual variability and the potential impact of repeated clipping and previous aneurysmal rupture. Results Eighty-six temporary clippings (from 20 patients) were recorded with a mean duration of 140.8 (41 − 238) seconds. Temporary arterial occlusion at the M1 segment of the middle cerebral artery produced specifically shaped trajectories, characterized by a preclipping PbtO2 level, rapid downward sigmoid-shaped curve, succession of progressively angled slopes, and lower plateau. The steepest slope of the curve correlated strongly with PbtO2 range (P Conclusions The effects of temporary arterial occlusion on temporal lobe oxygenation demonstrate a high degree of singularity, highlighting the potential benefits of assessing individual available collateral circulation intraoperatively. The “PbtO2 steepest slope” predicted the severity of PbtO2 decrease and was available within the first minute.

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attri- bution 4.0 International License, which permits use, sharing, adapta- tion, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/., Purpose: There is limited data concerning neuroimaging findings and longitudinal evaluation of familial cerebral cavernous malformations (FCCM) in children. Our aim was to study the natural history of pediatric FCCM, with an emphasis on symptomatic hemorrhagic events and associated clinical and imaging risk factors. Methods: We retrospectively reviewed all children diagnosed with FCCM in four tertiary pediatric hospitals between January 2010 and March 2022. Subjects with first available brain MRI and [Formula: see text] 3 months of clinical follow-up were included. Neuroimaging studies were reviewed, and clinical data collected. Annual symptomatic hemorrhage risk rates and cumulative risks were calculated using survival analysis and predictors of symptomatic hemorrhagic identified using regression analysis. Results: Forty-one children (53.7% males) were included, of whom 15 (36.3%) presenting with symptomatic hemorrhage. Seven symptomatic hemorrhages occurred during 140.5 person-years of follow-up, yielding a 5-year annual hemorrhage rate of 5.0% per person-year. The 1-, 2-, and 5-year cumulative risks of symptomatic hemorrhage were 7.3%, 14.6%, and 17.1%, respectively. The latter was higher in children with prior symptomatic hemorrhage (33.3%), CCM2 genotype (33.3%), and positive family history (20.7%). Number of brainstem (adjusted hazard ratio [HR] = 1.37, P = 0.005) and posterior fossa (adjusted HR = 1.64, P = 0.004) CCM at first brain MRI were significant independent predictors of prospective symptomatic hemorrhage. Conclusion: The 5-year annual and cumulative symptomatic hemorrhagic risk in our pediatric FCCM cohort equals the overall risk described in children and adults with all types of CCM. Imaging features at first brain MRI may help to predict potential symptomatic hemorrhage at 5-year follow-up.

Patient reported outcome measures (PROMs) are of utmost importance to clinical practice as they permit a patient-focused evaluation of surgical outcomes. However, recall bias can limit an adequate interpretation of PROMs.To assess the impact of recall bias of preoperative status on postoperative PROMs of patients submitted to surgery due to degenerative spine disease.Randomized controlled trial in a tertiary care neurosurgical unit in Portugal PATIENT SAMPLE: All patients submitted to surgery at our institution from January 2019 to April 2020 due to degenerative lumbar or cervical spine disease with valid PROMs questionnaires were enrolled, and 2 computer generated randomized groups were created.The study´s primary endpoint was the median postoperative Core Outcome Measure Index (COMI) score.The intervention group was sent postoperative questionnaires including preoperative answers, while patients in the control group were sent the same PROMs without the preoperative answers.Randomization was applied to 236 patients (118 for each group) and valid results were obtained for 147 patients (81 lumbar, 44 from the intervention group; and 66 cervical, 29 from the intervention group), from which 88 (60%) were females, with a median age of 58 years. Both groups shared similar baseline clinical characteristics and preoperative scores. Median postoperative COMI scores and interquartile ranges (IQR) were 4.20 (IQR: 2.30-6.00) and 5.45 (IQR: 3.75-7.40) for the intervention and control groups, respectively (Wilcoxon, p=.02). This difference was reached mainly due to cervical spine patients as median postoperative COMI score was 3.95 (IQR: 2.20-5.32) in the intervention group and 5.1 (IQR: 4.0-8.4) in the control group (Wilcoxon, p=.01). No significant difference was reached for lumbar patients.Better PROMs scores were obtained for degenerative cervical spine patients to whom the preoperative results were provided. Therefore, providing preoperative scores to patients upon postoperative PROMs fulfilment might influence postoperative results. Further research is necessary to increase the reliability of PROMs in clinical practice.

Introduction: Resistant bacterial infections following brain and spine surgery and spontaneous mucormycosis with central nervous system (CNS) involvement represent a serious treatment challenge and more efficient therapeutic approaches ought to be considered. Hyperbaric oxygen treatment (HBOT) has shown promise as a complementary therapy. This case series evaluated whether HBOT contributed to infection resolution in seven patients with refractory CNS infectious conditions. Methods: Clinical results for seven patients referred for HBOT between 2010 to 2018 to treat refractory postoperative brain and spine infections or spontaneously developing mucormycosis were retrospectively analysed. The patients’ clinical files and follow-up consultations were reviewed to assess evolution and outcome. Results: Seven patients were referred with a median age of 56 years. The median follow-up was 20 months. Four patients had postoperative infections and three had rhino-orbital-cerebral mucormycosis (ROCM). HBOT was used as an adjunctive treatment to antimicrobial therapy in all patients. Prior to HBOT, all patients had undergone an average of four operations due to infection refractoriness and had completed an average of five months of antimicrobial therapy. After HBOT, infection resolution was obtained in six patients without additional operations, while one patient with ROCM stopped HBOT after the third session due to intolerance. Three patients stopped antimicrobial therapy while four were maintained on prophylactic treatment. Conclusions: Infection resolution was reached in the six patients that completed HBOT as prescribed. HBOT may serve as an effective complementary treatment in CNS refractory postoperative and spontaneous infections.

Glioblastoma prognosis remains dismal despite gross total removal (GTR) followed by chemoradiotherapy. Other known prognostic factors include functional status, age and IDH mutation status. However, to improve patient outcome, a search for other features with impact on survival is needed. We aimed to analyse the impact of body mass index (BMI) on overall survival (OS) and progression-free survival (PFS) of surgically resected primary glioblastoma and evaluate if BMI constitutes an independent prognostic factor. We analysed all adult glioblastoma patients who underwent surgery and chemoradiotherapy between 2011 and 2017 at our institution. Overall survival was the study—primary endpoint, and progression-free survival—the secondary endpoint. We assayed age, gender, histology, extent of resection, IDH, functional and smoking status, cardiovascular risk factors, BMI, OS and PFS. Univariate analysis was conducted followed by multivariate analysis to establish independent prognostic factors. In accordance with the World Health Organization (WHO) BMI stratification, survival curves were obtained for normal-weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2) and obese (≥ 30 kg/m2) patient subgroups in addition to the non-obese (18.5–29.9 kg/m2) population. 193 patients were evaluated, with a median follow-up time of 17.3 months. Median OS was 21.3 months in obese patients vs 16.2 months in the non-obese (p = 0.017) and 16 months in the normal weight (p = 0.007). Higher median OS was also observed in patients under 60 and those in which GTR was obtained. Median PFS in obese individuals was 9 months in comparison to 6 months in the normal-weight subgroup (p = 0.04) and 7 months in the non-obese (p = 0.050). Multivariate analysis identified age

Ephaptic transmission has been proven as an alternative to chemical synaptic neural transmission and occurs in pathological situations, such as epilepsy and demyelination. Hereby, we report the case of an adult male that in 2012 was involved in a low-speed motorcycle accident with sacrum impact that from day three onwards reported unwanted penile movement when performing hallux and toe plantar flexion of the right foot. Urologic studies and perineal MRI were unremarkable but sacral MRI showed a significantly stenotic canal at the S1-S2 level while EMG displayed chronic moderate right S2 radiculopathy. Nine years later the patient underwent surgical decompression of the sacral canal with complete resolution of the synkinesis. We hypothesize ephaptic transmission between adjacent motor nerve fibres at the S2 sacral nerve root to be the likely mechanism explaining this phenomenon.

The aim of this study is to determine if there is a relation between preoperative sagittal alignment, based on radiographic parameters, and clinical outcomes, after lumbar decompressive procedures, in patients with lumbar spinal stenosis (LSS). This study enrolled patients with LSS who underwent lumbar decompressive procedures, between January 2016 and December 2017. Preoperative spinopelvic parameters were measured, and patients were divided into radiological groups according to the median of the following variables: relative lumbar lordosis (measured minus ideal lumbar lordosis), relative pelvic tilt (measured minus ideal pelvic tilt) and sagittal vertical axis (SVA). Clinical outcomes were compared between these groups and included the Core Outcome Measures Index, EuroQoL Five Dimension Questionnaire (EQ-5D) and Oswestry Disability Index (ODI) scores before and 1 year after surgery. Further correlation statistics between sagittal radiological measurements and the postoperative outcome scores were performed. The study included 104 patients. We did not find any clinically important difference in clinical outcomes between radiological groups. However, in correlation analyses we found a significant but weak statistical correlation between relative lumbar lordosis and both preoperative and postoperative ODI, as well as a significant statistical negative correlation between SVA and postoperative EQ-5D. Preoperative spinopelvic parameters did not significantly correlate with clinical outcomes after decompression surgery for LSS on non-deformity patients. Patients had a comparable improvement after surgery, regardless of their preoperative sagittal alignment.

Myxoid mesenchymal tumours harbouring fusions between EWSR1 and the CREB family transcription factors have recently been described. Whether they represent a novel entity or a myxoid variant of angiomatoid fibrous histiocytoma (AFH) remains a matter of debate. We describe the case of a 58-year-old woman with a previous history of breast cancer that developed progressive neurological decline due to a large mass located in the left lateral ventricle of the brain. Histology revealed a mesenchymal tumour with multinodular growth, variable cellularity, prominent myxoid stroma and numerous amianthoid fibres. No evidence of pseudo-capsule or lymphoid cuffing was identified. RNA sequencing disclosed EWSR1-CREB1 gene fusion. Only 20 cases of intracranial mesenchymal tumours harbouring these translocations have been described, mostly in adolescents and young adults and with dural attachment. Occurrence in this age group and with intraventricular location has been even more rarely reported. A better understanding of tumour behaviour is needed to establish treatment guidelines and improve patient outcome.