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Perioperative management of patients with sellar lesion submitted to endoscopic transsphenoidal neurosurgery (TSS) lacks standardization and therefore it is committed to each center clinical practice. Although neurosurgical procedure remains the same for all sellar lesions, perioperative approach can require different measures depending on the underlying disease. With the aim of standardizing our perioperative procedures and sharing our experience with other centers involved in the management of pituitary disease, we developed a clinical care path for patients with sellar lesions candidate to endoscopic TSS. For the drafting of the following protocol, the national and international guidelines published in the last 5 years have been evaluated and integrated with our center experience accumulated in decades of clinical practice. A steering committee including medical doctors involved in management of patients with pituitary masses at the Padua Hospital reviewed current knowledge on this topic. The committee developed a first draft which was shared with a broader group of medical doctors to reach a preliminary consensus; when it was reached, the clinical care assistance pathway was confirmed, validated, and published in the local web-based health service. We want to present and share our experience with colleagues involved in the perioperative management of pituitary diseases in other centers. [ABSTRACT FROM AUTHOR]

Postoperative infections after spinal surgery are a challenging issue, difficult to diagnose and treat, that requires prolonged medical therapy and even surgery. In this paper, we aim to review the current standards in the diagnosis and treatment of post-procedural Spondylodiscitis (SD). We performed a review of the available literature focusing on diagnostic and therapeutic standards of post-procedural SD, both after minimally invasive procedures and open surgery. Spinal infections can occur in less invasive procedures with an incidence ranging from 0.26% to 2.75%. Post-surgical spinal infections range from 2.1% to 8.5% for instrumented surgery, whereas these are less than 1% in open surgery without instrumentation. MRI is currently the most sensitive and specific technique to diagnose postoperative SD. CT guided aspiration culture should be performed in all patients with deep-seated infections with negative blood cultures. Early infections start with wound healing problems within a few weeks from surgery, and the occurrence of fever and an increase in serum markers of inflammation. Late infections often cause chronic pain, implant failure, non-union or wound dehiscence even a long time after surgery. The onset of the infection differentiates the specific treatment. Indeed, in the early postoperative period spinal fusion is not appropriate yet, and the stability of the fusion site only relies on the instrumentation. Therefore, even when suitable, implant removal may lead to undesirable consequences. In chronic infections, on the other hand, implant removal is unlikely to determine instability since the fusion has already been accomplished. [ABSTRACT FROM AUTHOR]

Objective: Glucose-dependent insulinotropic polypeptide receptor (GIPR) overexpression has been recently described in a proportion of gsp- somatotropinomas and suggested to be associated with the paradoxical increase of GH (GH-PI) during an oral glucose load. Design and methods: This study was aimed at linking the GIP/GIPR pathway to GH secretion in 25 somatotropinomasderived primary cultures and correlating molecular with clinical features in acromegalic patients. Given the impairment of the GIP/GIPR axis in acromegaly, an additional aim was to assess the effect of GH/IGF-1 stimulation on GIP expression in the enteroendocrine cell line STC-1. Results: Nearly 80% of GIPR-expressing somatotropinomas, all of them negative for gsp mutations, show increased GH secretion upon GIP stimulation, higher sensitivity to Forskolin but not to somatostatin analogs. Besides increased frequency of GH-PI, GIPR overexpression does not appear to affect acromegalic patients' clinical features. In STC-1 cells transfected with GIP promoter-driven luciferase vector, IGF-1 but not GH induced dose-dependent increase in luciferase activity. Conclusions: We demonstrate that GIPR mediates the GH-PI in a significant proportion of gsp- acromegalic patients. In these cases, the stimulatory effect of IGF-1 on GIP promoter support the hypothesis of a functional GH/IGF-1/GIP axis. Further studies based on larger cohorts and the development of a stable transgenic model with inducible GIPR overexpression targeted to pituitary somatotroph lineage will be mandatory to establish the real role of GIPR in the pathogenesis of somatotropinomas. [ABSTRACT FROM AUTHOR]

Relative radiometric normalization (RRN) minimizes radiometric differences among images caused by inconsistencies of acquisition condition. In this study, a cross-sensor RRN method is proposed for optical satellite images from Landsat 8 OLI (L8) and Landsat 7 ETM+ (L7) sensors. The data from these two sensors have different pixel depths. Therefore, a rescaling on the radiometry resolution is performed in the preprocessing. Then, multivariate alteration detection (MAD) based on kernel canonical correlation analysis (KCCA) is adopted, which is called KCCA-based MAD, to select pseudo-invariant features (PIFs). The process of RRN is performed by using polynomial regression with Gaussian weighted regression. In experiments, qualitative and quantitative analyses on images from different sensors are conducted. The experimental result demonstrates the superiority of the proposed nonlinear transformation, in terms of regression quality and radiometric consistency, compared with RRN using linear regression. [ABSTRACT FROM AUTHOR]

Central adrenal insufficiency (CAI) in acromegaly may be related to pituitary adenoma or induced by various medical treatments, transsphenoidal neurosurgery (TNS) or radiotherapy (RT), alone or combined. We assessed the role of all available treatments for acromegaly in inducing CAI. We retrospectively studied 97 patients. CAI was diagnosed if morning serum cortisol was < 138 nmol/l, or if its response was inadequate in the low-dose short synacthen test. Seventy-four subjects underwent TNS (and 17 of whom also underwent RT), and 23 were on primary medical therapy: overall we diagnosed 21 cases of CAI. Duration of acromegaly, invasion of cavernous sinus, disease control, and type of medical treatment were much the same for patients with and without CAI, which was identified in 18 % of patients (10/57) after one TNS, and in 53 % (9/17) after RT (p = 0.01); repeat surgery increased the risk of CAI (p = 0.02). The risk of CAI onset during the follow-up was lower among patients treated with TNS or medical therapy than after RT (p = 0.035). Medical treatment did not raise the risk of CAI, whereas a 5- and 4-fold higher risk of CAI was associated with repeat TNS and RT, respectively. Basal or stimulated cortisol levels were similar among acromegalic patients without CAI and matched controls with nonsecreting pituitary lesions. A significant proportion of patients with acromegaly developed CAI over time. While primary or secondary medical treatment did not contribute to the risk of CAI, repeat TNS and RT correlated with pituitary-adrenal axis impairment. [ABSTRACT FROM AUTHOR]

Purpose: Following limb amputation, central and peripheral nervous system relays partially maintain their functions and can be exploited for interfacing prostheses. The aim of this study is to investigate, for the first time by means of an EEG-TMS co-registration study, whether and how direct bidirectional connection between brain and hand prosthesis impacts on sensorimotor cortical topography. Methods: Within an experimental protocol for robotic hand control, a 26 years-old, left-hand amputated male was selected to have implanted four intrafascicular electrodes (tf-LIFEs-4) in the median and ulnar nerves of the stump for 4 weeks. Before tf-LIFE-4s implant (T0) and after the training period, once electrodes have been removed (T1), experimental subject's cortico-cortical excitability, connectivity and plasticity were tested via a neuronavigated EEG-TMS experiment. Results: The statistical analysis clearly demonstrated a significant modulation (with t-test p < 0.0001) of EEG activity between 30 and 100 ms post-stimulus for the stimulation of the right hemisphere. When studying individual latencies in that time range, a global amplitude modulation was found in most of the TMS-evoked potentials; particularly, the GEE analysis showed significant differences between T0 and T1 condition at 30 ms (p < 0.0404), 46 ms (p < 0.0001) and 60 ms (p < 0.007) latencies. Finally, also a clear local decrement in N46 amplitude over C4 was evident. No differences between conditions were observed for the stimulation of the left hemisphere. Conclusions: The results of this study confirm the hypothesis that bidirectional neural interface could redirect cortical areas -deprived of their original input/output functions- toward restorative neuroplasticity. This reorganization strongly involves bi-hemispheric networks and intracortical and transcortical modulation of GABAergic inhibition. [ABSTRACT FROM AUTHOR]

Background: Odontoid fractures are the most common odontoid injury and often cause atlantoaxial instability. Reports on postoperative status of patients who underwent surgery for such injuries are limited to small case series, and it is unclear whether any one technique produces better outcomes than another.Questions/purposes: We assessed the quality of the available literature for management of Type II odontoid fractures and surgery-related parameters, including surgical indications, clinical failure rate, and survivorship, postoperative ROM and function, neurologic deficits, complication and death rates, and radiographic healing rates related to either anterior dens screw or posterior C1-C2 fusion.Methods: We performed a systematic search in PubMed, Ovid, Cochrane Reviews, and Google Scholar databases. We used the methodology score proposed by Coleman et al. to rate study quality. Postoperative imaging bone union rates were extracted. Postoperative complications and neurologic impairment data were also collected.Results: Sixteen retrospective studies of overall low quality (average methodology score, 37.1) reporting a total of 518 patients were included. The methodology score and publication year were positively associated. The bone union rate approximated 83% (range, 33%-100%), with higher nonunion rates among patients older than 65 years. The death rate ranged widely (0%-28.6%) among different centers. Residual cervical pain was documented postoperatively from 10.5% to 26.7%, while survivorship ranged from 72% to 96.6%. No ROM data were reported.Conclusions: Current data on patients who had surgery for fracture of the dens did not allow us to establish superiority of one surgical approach over another. [ABSTRACT FROM AUTHOR]

The response to Prostaglandin (PG) E[SUB2] of T cells from gastric carcinoma (GC)and conjunctiva-basal cell carcinoma (conjunctiva-BCC)-bearing patients has been studied in relation to polyamine metabolism. Polyamines are crucial cofactors in cell growth as well as differentiation and many works report that lymphocyte spermine (SP), spermidine (SPD) and putrescine (PUT) levels may be related to tumor proliferation. The present work aims to detect the basal and PGE[SUB2] induced concentrations of these polyamines and cAMP, ornithine decarboxylase (ODC), spermine Nl-acetyltransferase (SAT) activities of T lymphocytes drawn from patients suffering from GC and conjunctivaBCC since many carcinomas are characterized by high levels of PGE[SUB2]. Data obtained from lymphocytes of neoplastic subjects were compared with those derived from PGE[SUB2]-treated control lymphocytes. Results highlight a very significant increase of all the polyamine metabolites in PGE[SUB2]-treated T cells from neoplastic patients in respect to the untreated and PGE[SUB2]-treated control lymphocytes. Therefore, it is conceivable that the PGE[SUB2] content increase, often occurring during the epithelial tumour development, may contribute, through enhancement of polyamine metabolism, to tumor progression. [ABSTRACT FROM AUTHOR]

Introduction: Vagus nerve stimulation (VNS) is a neuromodulation technique approved for Treatment-Resistant Depression (TRD). Evidence regarding its long-term efficacy and safety is still scarce. Objectives: To descriptively report a case series of 3 patients undergoing adjunctive VNS for TRD with an over 10-year follow-up. Methods: We investigated outcomes of clinical interest in patients with ongoing VNS for at least 10 years after the device implantation. They had participated in a larger single-arm interventional study conducted at the University Hospital of Padua. They were diagnosed with chronic unipolar (1), recurrent unipolar (1), and bipolar (1) TRD. Results: Our 3 cases had an average 14-year history of psychiatric disease before surgery. Afterward, all subjects achieved clinical remission within two years. 2 patients experienced relapses within the first 4 years of treatment (respectively, 1 and 2 episodes). The other case showed a recurrent trend of brief relapses every two years. Only 1 individual needed to be admitted to the psychiatric unit once. None of them committed suicidal attempts. Prescription of antidepressants remained almost unchanged after the first two years. 2 individuals improved and 1 maintained their working position. Common adverse events were voice alteration (3/3), neck pain (2/3), and cough (2/3). Conclusions: Very few cases of 10-year VNS for TRD have been reported so far. For our subjects, VNS was most likely to have a major impact on the clinical course of the disease. This treatment can be a safe and effective adjunctive intervention in a subgroup of patients with TRD. [ABSTRACT FROM AUTHOR]

Background: Previous studies showed a differential distribution of the four regulatory subunits of cAMP-dependent protein kinases inside the brain, that changed in rodent gliomas: therefore, the distribution of these proteins inside the brain can give information on the functional state of the cells. Our goal was to examine human brain tumors to provide evidence for a differential distribution of protein kinase A in different tumors.Methods: The distribution of detergent insoluble regulatory (R1 and R2) and catalytic subunits of cAMP dependent kinases was examined in pediatric brain tumors by immunohistochemistry and fluorescent cAMP analogues binding.Results: R2 is organized in large single dots in medulloblastomas, while it has a different appearance in other tumors. Fluorescent cAMP labelling was observed only in medulloblastoma.Conclusions: A different distribution of cAMP dependent protein kinases has been observed in medulloblastoma. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective case review of children with eosinophilic granuloma of the cervical spine. Objective: To present the clinical features, radiographic findings, management, and results of 7 pediatric patients with eosinophilic granuloma of the cervical spine. Summary Of Background Data: Management of the eosinophilic granuloma of the pediatric cervical spine is challenging, and must be adapted according to the patient, as no level I evidences have been produced. The therapeutic goals in these children are spinal stability, preservation of neurologic function, and relief of pain, always keeping in mind that patients are still growing. The localization in the cervical spine of children is extremely rare, with less than 50 patients reported in literature between 1966 and 2008. Methods: We reviewed the 7 pediatric patients with a diagnosis of eosinophilic granuloma of the cervical spine who were managed between 1970 and 1990 by the senior author. All patients presented with isolated cervical spine involvement, and all of them had a histologic diagnosis of eosinophilic granuloma (EG). All had open physes. Results: There were 5 boys and 2 girls (mean age: 10 years; range 4-16). We followed-up patients for 19 years (range 8-29). The symptoms at presentation varied according to the localization of the tumor in the cervical spine. Conclusion: Management of pediatric patients with EG of the cervical spine is challenging, especially when there is neurologic involvement. Observation alone, prolonged immobilization, systemic chemotherapy, curettage with or without bone grafting, corticosteroid injection, and low dose radiation therapy have been proposed for the management of patients with EG. Surgery is required when the child presents neurologic involvement. Children who received a vertebral interbody fusion can show, at long period follow-up, normal shape of the neck, with maintenance of the normal motion of the adjacent segments. [ABSTRACT FROM AUTHOR]

A large literature assessed the relationships between the O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation status and glioblastoma location with inconsistent results. Studies assessing this association using the percentage of methylation are lacking. This cross-sectional study aimed at investigating relationships between glioblastoma topology and MGMT promoter methylation, both as categorical (presence/absence) and continuous (percentage) status. We included patients with diagnosis of isocitrate dehydrogenase wild-type glioblastoma [World Health Organization (WHO) 2021 classification], available pre-surgical MRI, known MGMT promoter methylation status. Quantitative methylation assessment was obtained through pyrosequencing. Several analyses were performed for categorical and continuous variables ( χ 2 , t -tests, ANOVA and Pearson's correlations), investigating relationships between MGMT methylation and glioblastoma location in cortex/white matter/deep grey matter nuclei, lobes, left/right hemispheres and functional grey and white matter network templates. Furthermore, we assessed at the voxel-wise level location differences between (i) methylated and unmethylated glioblastomas and (ii) highly and lowly methylated glioblastomas. Lastly, we investigated the linear relationship between glioblastoma-voxel location and the MGMT methylation percentage. Ninety-three patients were included (66 males; mean age: 62.3 ± 11.3 years), and 42 were MGMT methylated. The mean methylation level was 33.9 ± 18.3%. No differences in glioblastoma volume and location were found between MGMT-methylated and MGMT-unmethylated patients. No specific anatomical regions were associated with MGMT methylation at the voxel-wise level. MGMT methylation percentage positively correlated with cortical localization ( R = 0.36, P = 0.021) and negatively with deep grey matter nuclei localization ( R = -0.35, P = 0.025). To summarize, we investigated relationships between MGMT methylation status and glioblastoma location through multiple approaches, including voxel-wise analyses. In conclusion, MGMT promoter methylation percentage positively correlated with cortical glioblastoma location, while no specific anatomical regions were associated with MGMT methylation status., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Transsphenoidal surgery is the treatment of choice for Cushing's disease. Successful surgery is associated with subnormal postoperative serum cortisol concentrations and cortisoluria levels, which may guide decisions regarding immediate reoperation. Remission is defined as the biochemical reversal of hypercortisolism with the re-emergence of diurnal circadian rhythm., Methods: A single-center prospective cohort study was conducted among thirty-three patients who underwent transsphenoidal pituitary surgery for Cushing's disease. Postoperative surgical outcomes, daily morning cortisolemia, and 24 h urinary-free cortisol from the first to the fifth morning were evaluated., Results: All patients underwent surgery, with a remission rate of 81.2%. Of the 26 patients who achieved early remission, 92% remained in remission. Two patients (7.7%) showed recurrence of Cushing's disease during a mean follow-up of 81.7 months. Early postoperative hypocortisolism suggests complete removal of the tumor, correlating with high rates of remission ( p < 0.001). Also, in 12.5% of patients with early cortisol values >138 nmol/L, there was a gradual late remission., Conclusions: In our cohort of patients, the endoscopic transsphenoidal approach was safe and effective in the treatment of Cushing's disease. We demonstrated that serum and urinary cortisol concentrations did not experience significant fluctuations from the first to the fifth day. This constitutes an accurate predictor of durable remission, comprising a distinctive finding in the intermediate term by our team.

Study Design: Epidemiological study., Objective: This study aimed to evaluate the annual incidence of spondylolisthesis requiring surgery in Italy and the epidemiological characteristics of the patients., Background: The health care system continues to incur considerable costs as a result of low-back pain. Segmental instability of the lumbar spine has attracted significant interest from researchers as a potential mechanism leading to mechanical low back pain., Materials and Methods: The Italian Ministry of Health's National Hospital Discharge Reports database in the 2001-2016 period was considered., Results: A total of 55,804 hospital admissions for spondylolisthesis were performed in Italy. The cumulative incidence was 6.8 interventions for every 100,000 Italian adult residents. The highest amount of procedures was recorded in the 65-69 years of age group. The overall patient's age was 56.8 ± 15.1 years. The 62.2% of patients were females. The average hospital stay length was 8.1 ± 7.3 days. On average, older patients require more days of hospital stay. Over the study period, it was observed a decreasing trend in the average number of days of hospital stay. The main primary diagnoses included were "acquired spondylolisthesis" [International Classification of Diseases (ICD) code: 738.4; 57.8%] and "spondylolisthesis" (ICD code: 756.12; 42.2%). By far, the main primary procedure performed was "lumbar and lumbosacral fusion of the anterior column, posterior technique" (ICD code: 81.08; 60.3%)., Conclusions: Spondylolisthesis is a problem in Italy and a leading cause requiring spine surgery. Females were the majority of patients requiring surgery for spondylolisthesis. However, for younger age groups, males showed superior or equal need for spine surgery. The socioeconomic impact of spondylolisthesis in Italy is relevant, affecting patients still in the working population. The increasing trend of spine surgery for spondylolisthesis in Italy may be attributable to the widespread diffusion of modern diagnostic and surgical technologies., Level of Evidence: Level II., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Lesion network mapping (LNM) is a popular framework to assess clinical syndromes following brain injury. The classical approach involves embedding lesions from patients into a normative functional connectome and using the corresponding functional maps as proxies for disconnections. However, previous studies indicated limited predictive power of this approach in behavioral deficits. We hypothesized similarly low predictiveness for overall survival (OS) in glioblastoma (GBM)., Methods: A retrospective dataset of patients with GBM was included (n = 99). Lesion masks were registered in the normative space to compute disconnectivity maps. The brain functional normative connectome consisted in data from 173 healthy subjects obtained from the Human Connectome Project. A modified version of the LNM was then applied to core regions of GBM masks. Linear regression, classification, and principal component (PCA) analyses were conducted to explore the relationship between disconnectivity and OS. OS was considered both as continuous and categorical (low, intermediate, and high survival) variable., Results: The results revealed no significant associations between OS and network disconnection strength when analyzed at both voxel-wise and classification levels. Moreover, patients stratified into different OS groups did not exhibit significant differences in network connectivity patterns. The spatial similarity among the first PCA of network maps for each OS group suggested a lack of distinctive network patterns associated with survival duration., Conclusions: Compared with indirect structural measures, functional indirect mapping does not provide significant predictive power for OS in patients with GBM. These findings are consistent with previous research that demonstrated the limitations of indirect functional measures in predicting clinical outcomes, underscoring the need for more comprehensive methodologies and a deeper understanding of the factors influencing clinical outcomes in this challenging disease., Competing Interests: Declaration of competing interest Drs Salvalaggio and Pini and Prof Corbetta reported a patent pending (102022000015360). No other disclosures are reported., (Copyright © 2023. Published by Elsevier Inc.)

Background: Little is known about prognostic factors of brain metastases (BM) from colorectal cancer (CRC). HER2 amplification/overexpression (HER2+) was previously described; its impact on prognosis remains uncertain., Methods: In the translational study HEROES, extensive molecular analysis was performed on primary CRC (prCRC) and their matched resected BM by means of NGS comprehensive genomic profiling and HER2 status as assessed by immunohistochemical/ in situ hybridization. Count of tumour-infiltrating lymphocytes (TILs) was also performed., Primary Objective: to describe the molecular landscape of paired BM/prCRC., Secondary Objectives: to search for new prognostic biomarkers of outcome after BM resection: intracranial-only Progression-Free Survival (BM-iPFS), Progression-Free Survival (BM-PFS), and Overall Survival (BM-OS)., Results: Out of 22 patients having paired samples of prCRC and BM, HER2+ was found on 4 (18%) BM, 3 (75%) of which also HER2+ in matched prCRC. Lower tumour mutation burden (HR 3.08; 95%CI 1.06-8.93; p = 0.0386) and HER2-negative BM (HER2neg) (HR 7.75;95%CI 1.97-30.40; p = 0.0033) were associated with longer BM-iPFS; HER2neg BM (HR 3.44; 95%CI 1.03-11.53; p = 0.0449) and KRAS mut BM (HR 0.31; 95%CI 0.12-0.80; p = 0.0153) conferred longer BM-PFS. Longer BM-OS was found in pts with TILs-enriched (≥1.6/HPF) BM (HR 0.11; 95%CI0.01-0.91; p = 0.0403)., Conclusions: This study shows HER2+ enrichment in both BM and their prCRC. TILs-enriched BM conferred better BM-OS., (© 2024. The Author(s).)

Metastases are complications of primary tumors due to prolonged cancer survival and have become an important issue for oncological patients and the most frequent cause of death and disability. Bone metastases occur at a later stage of cancer disease, and the spine is the most frequent site. To date, the aim of the treatment of metastases remains to be the control of disease and provide a satisfactory quality of life. The decision making of treatment is influenced by several factors such as the status of the primary disease, the number of metastases, site involvement, and the performance status of the patients. For this reason, the treatment of metastases is challenging and undergoes constant development. Therefore, alternative techniques with respect to surgery, which is the first option but not always practicable, and radiochemotherapy are attractive. Lately, electrochemotherapy has emerged as an innovative method for treating various primary and metastatic solid tumors, showing promising outcomes in terms of inducing tumor tissue necrosis and alleviating symptoms. This technique uses electric pulses to increase the uptake of chemotherapy by tumor cells. Despite the initial enthusiasm and good results in the treatment of bone tumors, relatively few papers have described its use in spine metastases. Therefore, we conducted a systemic review of this intriguing topic while also reporting our experience in the use of electrochemotherapy for the treatment of spine metastases.

Background: Status epilepticus is a life-threatening condition that is defined as refractory (RSE) when the seizure activity continues despite treatment with benzodiazepine and a second appropriate treatment. Super refractory status epilepticus (SRSE) is an RSE that persists or recurs for ≥24 h. Few papers have reported the outcomes of pediatric patients affected by RSE and SRSE and treated with neuromodulation therapies. Vagus nerve stimulation (VNS) is an approved treatment for drug-resistant epilepsy. We present our findings of pediatric patients treated with VNS for RSE/SRSE., Methods: We present a case series of seven consecutive pediatric patients treated with VNS for SRSE since 2012 by a single surgeon in Monza and Padua. A rapid titration was started soon after implantation. We considered electroclinical data before and after VNS implantation and at the last follow-up., Results: We achieved the resolution of SRSE in five out of seven patients in a mean time of two weeks. At the last follow-up, these patients had a significant reduction of seizure burden without any relapse of SE., Discussion and Conclusions: Based on our limited findings, we discuss the potential role of VNS therapy in similar but distinct clinical contexts. For patients with drug-resistant epilepsy and RSE/SRSE, prompt VNS consideration is suggested, offering rapid responses and potentially reducing pharmacological load. Meanwhile, in NORSE/FIRES, we suggest early neuromodulation during the acute phase if standard treatments prove ineffective or not tolerated. This approach may leverage VNS's potential anti-inflammatory effects and neuromodulation, enhancing patient-specific treatments. Expanding case studies and prolonged follow-ups are recommended to strengthen these clinical insights.

Introduction: Vagus nerve stimulation (VNS) is a neuromodulation therapy for drug-resistant epilepsy (DRE), refractory status epilepticus, and treatment-resistant depression. The lead is tunneled into the subcutaneous space and connected to the generator, which is usually implanted in a subcutaneous pocket below the clavicle. Surgical complications in the chest region include skin breakdown or infection. An alternative approach is to perform a subclavear subpectoral implantation. In our surgical series, we report a new aesthetic implantation method for VNS generators in children and young patients: the transaxillary subpectoral placement., Materials and Methods: From May 2021 to May 2023, 10 vagus nerve stimulation generators were placed subpectorally with a transaxillary approach by the authors. We considered operative time, surgical complications such as blood loss, infections, device migration, pain, and adverse events at follow-up., Results: In this surgical series, we reviewed all cases of subpectoral implantation of VNS generators in children and young adults at our institution in the last 2 years. All patients were treated with subpectoral Sentiva 1000 (Livanova PLC) insertion with axillary access by a neurosurgeon and a pediatric surgeon. The operative time was slightly longer compared to the traditional subcutaneous implant. All generators reported impedances within the optimal range. Blood loss was not significant and no other perioperative complications were reported. Patients and families were highly satisfied with the outcomes in terms of comfort and aesthetic results after surgery and at the last follow-up. No cases of infection occurred, and no malfunctions or displacements of the generator were registered at clinical follow-up., Conclusion: The transaxillary subpectoral placement of theVNS generator is an aesthetic and anatomic approach, which provides several benefits to children and young adults., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Context: Cushing's disease (CD) is rare condition burdened by several systemic complications correlated to higher mortality rates. The primary goal of clinicians is to achieve remission, but it is unclear if treatment can also increase life expectancy., Aim: To assess the prevalence of cortisol-related complications and mortality in a large cohort of CD patients attending a single referral centre., Materials and Methods: The clinical charts of CD patients attending a referral hospital between 2001 and 2021 were reviewed., Results: 126 CD patients (median age at diagnosis 39 years) were included. At the last examination, 78/126 (61.9%) of the patients were in remission regardless of previous treatment strategies. Patients in remission showed a significant improvement in all the cardiovascular (CV) comorbidities (p < 0.05). The CV events were more frequent in older patients (p = 0.003), smokers and persistent CD groups (p < 0.05). Most of the thromboembolic (TE) and infective events occurred during active stages of the disease. The CV events were the most frequent cause of death. The standardized mortality ratio (SMR) resulted increased in persistent cases at the last follow-up (SMR 4.99, 95%CI [2.15; 9.83], p < 0.001) whilst it was not higher in those in remission (SMR 1.66, 95%CI [0.34; 4.85], p = 0.543) regardless of the timing or number of treatments carried out. A younger age at diagnosis (p = 0.005), a microadenoma (p = 0.002), and remission status at the last follow-up (p = 0.027) all increased survival. Furthermore, an elevated number of comorbidities, in particular arterial hypertension, increased mortality rates., Conclusions: Patients with active CD presented a poor survival outcome. Remission restored the patients' life expectancy regardless of the timing or the types of treatments used to achieve it. Persistent CD-related comorbidities remained major risk factors., (© 2023. The Author(s).)

Background : Thalamopeduncular tumors are challenging lesions arising at the junction between the thalamus and the cerebral peduncle. They represent 1-5% of pediatric brain tumors, are mainly pilocytic astrocytoma and occur within the first two decades of life. To date, the optimal treatment remains unclear. Methods : We retrospectively reviewed pediatric patients who underwent surgery for thalamopeduncular tumors in the Academic Pediatric Neurosurgery Unit of Padova and Verona from 2005 to 2022. We collected information on age, sex, symptoms, preoperative and postoperative neuroradiological studies, histological specimens, surgical approaches, and follow-up. Results : We identified eight patients with a mean age of 9 years. All lesions were pilocytic astrocytoma. The main symptoms were spastic hemiparesis, cranial nerve palsy, headache, and ataxia. The corticospinal tract was studied in all patients using diffusion-tensor imaging brain MRI and in two patients using navigated transcranial magnetic stimulation. The transsylvian approach was the most frequently used. A gross total resection was achieved in two patients, a subtotal resection in five and a partial resection in one. In three patients, a second treatment was performed due to the regrowth of the tumor, performing an additional surgery in two cases and a second-look surgery followed by adjuvant therapy in one. After the surgery, four patients maintained stability in their postoperative neurological exam, two patients improved, and two worsened but in one of them, an improvement during recovery occurred. At the last follow-up available, three patients were disease-free, four had a stable tumor residual, and only one patient died from the progression of the disease. Conclusions : Advanced preoperative tools allow one to define a safe surgical strategy. Due to the indolent behavior of thalamopeduncular tumors, surgery should be encouraged.

Background: Resting-state functional-MRI studies identified several cortical gray matter functional networks (GMNs) and white matter functional networks (WMNs) with precise anatomical localization. Here, we aimed at describing the relationships between brain's functional topological organization and glioblastoma (GBM) location. Furthermore, we assessed whether GBM distribution across these networks was associated with overall survival (OS)., Materials and Methods: We included patients with histopathological diagnosis of IDH-wildtype GBM, presurgical MRI and survival data. For each patient, we recorded clinical-prognostic variables. GBM core and edema were segmented and normalized to a standard space. Pre-existing functional connectivity-based atlases were used to define network parcellations: 17 GMNs and 12 WMNs were considered in particular. We computed the percentage of lesion overlap with GMNs and WMNs, both for core and edema. Differences between overlap percentages were assessed through descriptive statistics, ANOVA, post-hoc tests, Pearson's correlation tests and canonical correlations. Multiple linear and non-linear regression tests were employed to explore relationships with OS., Results: 99 patients were included (70 males, mean age 62  years). The most involved GMNs included ventral somatomotor, salient ventral attention and default-mode networks; the most involved WMNs were ventral frontoparietal tracts, deep frontal white matter, and superior longitudinal fasciculus system. Superior longitudinal fasciculus system and dorsal frontoparietal tracts were significantly more included in the edema ( p  < 0.001). 5 main patterns of GBM core distribution across functional networks were found, while edema localization was less classifiable. ANOVA showed significant differences between mean overlap percentages, separately for GMNs and WMNs ( p -values<0.0001). Core-N12 overlap predicts higher OS, although its inclusion does not increase the explained OS variance., Discussion and Conclusion: Both GBM core and edema preferentially overlap with specific GMNs and WMNs, especially associative networks, and GBM core follows five main distribution patterns. Some inter-related GMNs and WMNs were co-lesioned by GBM, suggesting that GBM distribution is not independent of the brain's structural and functional organization. Although the involvement of ventral frontoparietal tracts (N12) seems to have some role in predicting survival, network-topology information is overall scarcely informative about OS. fMRI-based approaches may more effectively demonstrate the effects of GBM on brain networks and survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest, (Copyright © 2023 Sansone, Pini, Salvalaggio, Gaiola, Volpin, Baro, Padovan, Anglani, Facchini, Chioffi, Zagonel, D’Avella, Denaro, Lombardi and Corbetta.)

Purpose: Regorafenib demonstrated encouraging results in recurrent glioblastoma patients. Some studies showed that changes in circulating thyroid hormones (fT3, fT4, fT3/fT4 ratio) can be considered as prognostic factors in patients with various types of tumors. We designed this study to investigate the relationship between baseline thyroid variables and outcome in IDH-wild type GBM patients who were treated with regorafenib., Methods: This multicenter retrospective study included recurrent IDH-wild-type glioblastoma patients treated with regorafenib. Only patients with baseline thyroid function values (TSH, fT3, fT4, fT3/fT4 ratio) available were evaluated. RANO criteria were used to analyze neuroradiological response. Survival curves were estimated using the Kaplan-Meier method. The relationships between baseline thyroid variables (TSH, fT3, fT4, fT3/fT4) and survival (PFS, OS) were investigated with Cox regression models., Results: From November 2015 to April 2022, 134 recurrent IDH-wildtype GBM patients were treated with regorafenib and 128 of these had information on baseline thyroid function value. Median follow-up was 8 months (IQR 4.7-14.0). Objective Response Rate was 9% and Disease Control Rate was 40.9%. Median PFS was 2.7 months (95%CI 2.2-3.6) and median OS was 10.0 months (95%CI 7.0-13.0). Lower baseline TSH value in the blood was correlated with a higher rate of disease progression to regorafenib (p = 0.04). Multivariable analyses suggested a non-linear relationship between PFS (p = 0.01) and OS (p = 0.03) with baseline fT3/fT4 ratio., Conclusion: In recurrent wild-type IDH glioblastoma patients, baseline fT3/fT4 ratio showed a non-linear relationship with survival, with different impacts across the spectrum of fT3/fT4 ratio. Moreover, baseline TSH may be a predictor of regorafenib activity., (© 2023. The Author(s).)

The glucose-dependent insulinotropic polypeptide receptor (GIPR) is aberrantly expressed in about one-third of GH-secreting pituitary adenomas (GH-PAs) and has been associated with a paradoxical increase of GH after a glucose load. The reason for such an overexpression has not yet been clarified. In this work, we aimed to evaluate whether locus-specific changes in DNA methylation patterns could contribute to this phenomenon. By cloning bisulfite-sequencing PCR, we compared the methylation pattern of the GIPR locus in GIPR-positive (GIPR + ) and GIPR-negative (GIPR - ) GH-PAs. Then, to assess the correlation between Gipr expression and locus methylation, we induced global DNA methylation changes by treating the lactosomatotroph GH3 cells with 5-aza-2'-deoxycytidine. Differences in methylation levels were observed between GIPR + and GIPR - GH-PAs, both within the promoter (31.9% vs. 68.2%, p < 0.05) and at two gene body regions (GB&#95;1 20.7% vs. 9.1%; GB&#95;2 51.2% vs. 65.8%, p < 0.05). GH3 cells treated with 5-aza-2'-deoxycytidine showed a ~75% reduction in Gipr steady-state level, possibly associated with the observed decrease in CpGs methylation. These results indicate that epigenetic regulation affects GIPR expression in GH-PAs, even though this possibly represents only a part of a much more complex regulatory mechanism.