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Chronic pain, such as low-back pain, can be a highly disabling condition degrading people's quality of life (QoL). Not every patient responds to pharmacological therapies, thus alternative treatments have to be developed. The chronicity of pain can lead to a somatic dysperception, meaning a mismatch between patients' own body perception and its actual physical state. Since clinical evaluation of pain relies on patients' subjective reports, a body image disruption can be associated with an incorrect pain rating inducing incorrect treatment and a possible risk of drug abuse. Our aim was to reduce chronic low-back pain through a multimodal neurorehabilitative strategy using innovative technologies to help patients regain a correct body image. Twenty patients with chronic low-back pain were included. Before and after treatment, patients underwent: a neurological exam; a neuro-psychological evaluation testing cognitive functions (memory, attention, executive functions) and personality traits, QoL and mood; pain ratings; sensorimotor functional abilities' testing. Patients underwent a 6 week-neurorehabilitative treatment (total 12 sessions) using virtual reality (VRRS system, Khymeia, Italy). Treatment consisted on teaching patients to execute correct movements with the painful body parts to regain a correct body image, based on the augmented multisensory feedback (auditory, visual) provided by the VRRS. Our data showed significant reductions in all pain rating scale scores (p<0.05); significant improvements of QoL in the domains of physical functioning, physical role functioning, bodily pain, vitality, and social role functioning; improvements in cognitive functions (p<0.05); improvements in functional scales (p<0.05) and mood (p = 0.04). This non-pharmacological approach was able to act on the multi-dimensional aspects of pain and improved patients' QoL, pain intensity, mood and patient's functional abilities.

Besides the pulmonary manifestations caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), an emerging endocrine phenotype, which can heavily impact on the severity of the syndrome, has been recently associated with coronavirus disease 2019 (COVID-19). Patients with pituitary diseases or the pituitary gland itself may also be involved in COVID-19 clinical presentation and/or severity, causing pituitary apoplexy.Moreover, hypopituitarism is frequently burdened by several metabolic complications, including arterial hypertension, hyperglycemia, obesity and vertebral fractures, which have all been associated with poor outcomes and increased mortality in patients infected by SARS-CoV-2.This review will discuss hypopituitarism as a condition that might have a bidirectional relationship with COVID-19 due to the frequent presence of metabolic comorbidities, to the direct or indirect pituitary damage or being per se a potential risk factor for COVID-19. Finally, we will address the current recommendations for the clinical management of vaccines in patients with hypopituitarism and adrenal insufficiency.

The accuracy of target delineation in radiation treatment (RT) planning of cerebral gliomas is crucial to achieve high tumor control, while minimizing treatment-related toxicity. Conventional magnetic resonance imaging (MRI), including contrast-enhanced T1-weighted and fluid-attenuated inversion recovery (FLAIR) sequences, represents the current standard imaging modality for target volume delineation of gliomas. However, conventional sequences have limited capability to discriminate treatment-related changes from viable tumors, owing to the low specificity of increased blood-brain barrier permeability and peritumoral edema. Advanced physiology-based MRI techniques, such as MR spectroscopy, diffusion MRI and perfusion MRI, have been developed for the biological characterization of gliomas and may circumvent these limitations, providing additional metabolic, structural, and hemodynamic information for treatment planning and monitoring. Radionuclide imaging techniques, such as positron emission tomography (PET) with amino acid radiopharmaceuticals, are also increasingly used in the workup of primary brain tumors, and their integration in RT planning is being evaluated in specialized centers. This review focuses on the basic principles and clinical results of advanced MRI and PET imaging techniques that have promise as a complement to RT planning of gliomas.

BackgroundParkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting both motor and non-motor systems. Deep brain stimulation of the subthalamic nucleus (STN-DBS) has been an approved treatment for PD for more than 30 years, but few data are available regarding its long-term effectiveness.ObjectiveThe aim of this study is to evaluate patients’ outcome, both from a motor and non-motor perspective, 9 to 14 years after DBS implantation. We have investigated patients with advanced PD and treated with STN-DBS, in relation to key clinical features of PD.Methods18 patients were assessed both retrospectively and prospectively. They underwent motor examination, neuropsychological evaluation and questionnaires on the quality of life, preoperatively, as well as 1, 9 and 14 years after DBS surgery. All patients were implanted with STN-DBS at San Raffaele Hospital between 2004 and 2010.Results13 males and five females underwent DBS implantation with a mean PD duration of 11 years. Stimulation significantly improved med-off/stim-on condition up to 9 years, compared to the preoperative off state, and med-on/stim-on condition at 14 years, compared to med-on/stim-off state. Long term improvement specifically involved tremor and rigidity, as well as dopaminergic daily dose. At the same time, STN-DBS had no long-lasting effect on axial symptoms and cognitive functions.ConclusionsSTN-DBS remains an effective therapy for advanced PD, also over the years. Despite the underlying progression of the disease, this treatment extends the period in which the overall quality of life is still acceptable.

BackgroundThoracic disc herniation (TDH) is a rare condition with severe neurological sequelae. Surgical management is still a matter of debate and challenging.MethodWe present a modification of the transdural approach for TDH. The approach has been described in a stepwise fashion, analysing pre-, peri-, and postoperative strategies to improve patients’ management and reduce approach-related morbidity.ConclusionThe modified posterior transdural approach represents an effective technique for TDH, minimizing the risk of spinal cord damages, which can dramatically affect the outcome.

PurposePatients suffering from craniopharyngiomas currently have good survival rates, but long-term sequelae, such as development of obesity, worsen their quality of life. Optimal treatment is still controversial and changed during the decades, becoming less aggressive. Transcranial (TC) surgery was the first approach to be used, followed by extended transsphenoidal (eTNS) access. This study aims to compare the two approaches in terms of risk of hypothalamic damage leading to obesity.MethodsThis is a monocentric retrospective analysis of post-puberal patients treated for primary craniopharyngioma. Postoperative obesity and percentual postsurgical BMI variation were considered proxy for hypothalamic function and used to fit regression models with basal BMI, type of surgery, tumor volume and hypothalamic involvement (anterior vs. anteroposterior).ResultsNo difference in radicality was observed between the two approaches; eTNS was more effective in ameliorating visual function but was significantly associated with CSF leaks. The TC approach was associated with a higher incidence of diabetes insipidus. Regression analysis showed only tumor volume and basal BMI resulted as independent predictors for both postoperative obesity (respectively, OR 1.15, P = 0.041, and OR 1.57, P < 0.001) and percentual BMI variation (respectively, + 0.92%, P = 0.005, and − 1.49%, P = 0.001).ConclusionsLarger lesions portend a higher risk to develop postoperative obesity, independently of hypothalamic involvement. Interestingly, basal BMI is independent of lesional volume and is associated with postoperative obesity, but lesser postoperative BMI variation. The surgical approach does not influence the obesity risk. However, eTNS proves valid in managing large tumors with important hypothalamic invasion.

Achaete-scute homolog 1 gene (ASCL1) is a gene classifier for the proneural (PN) transcriptional subgroup of glioblastoma (GBM) that has a relevant role in the neuronal-like differentiation of GBM cancer stem cells (CSCs) through the activation of a PN gene signature. Besides prototypical ASCL1 PN target genes, the molecular effectors mediating ASCL1 function in regulating GBM differentiation and, most relevantly, subgroup specification are currently unknown. Here we report that ASCL1 not only promotes the acquisition of a PN phenotype in CSCs by inducing a glial-to-neuronal lineage switch but also concomitantly represses mesenchymal (MES) features by directly downregulating the expression of N-Myc downstream-regulated gene 1 (NDRG1), which we propose as a novel gene classifier of MES GBMs. Increasing the expression of ASCL1 in PN CSCs results in suppression of self-renewal, promotion of differentiation and, most significantly, decrease in tumorigenesis, which is also reproduced by NDRG1 silencing. Conversely, both abrogation of ASCL1 expression in PN CSCs and enforcement of NDRG1 expression in either PN or MES CSCs induce proneural-to-mesenchymal transition (PMT) and enhanced mesenchymal features. Surprisingly, ASCL1 overexpression in MES CSCs increases malignant features and gives rise to a neuroendocrine-like secretory phenotype. Altogether, our results propose that the fine interplay between ASCL1 and its target NDRG1 might serve as potential subgroup-specific targetable vulnerability in GBM; enhancing ASCL1 expression in PN GBMs might reduce tumorigenesis, whereas repressing NDRG1 expression might be actionable to hamper the malignancy of GBM belonging to the MES subgroup.

Brain injury and cerebral vasospasm during the 14 days after the subarachnoid hemorrhage (SAH) are considered the leading causes of poor outcomes. The primary injury induces a cascade of events, including increased intracranial pressure, cerebral vasospasm and ischemia, glutamate excitotoxicity, and neuronal cell death. The objective of this study was to monitor the time course of glutamate, and associated enzymes, such as glutamate–oxaloacetate transaminase (GOT1), glutamate-pyruvate transaminase (GPT) in cerebrospinal fluid (CSF) and serum, shortly after SAH, and to assess their prognostic value. A total of 74 participants participated in this study: 45 participants with SAH and 29 controls. Serum and CSF were sampled up to 14 days after SAH. SAH participants' clinical and neurological status were assessed at hospitalization, at discharge from the hospital, and 3 months after SAH. Furthermore, a logistic regression analysis was carried out to evaluate the ability of GOT1 and glutamate levels to predict neurological outcomes. Our results demonstrated consistently elevated serum and CSF glutamate levels after SAH. Furthermore, serum glutamate level was significantly higher in patients with cerebral ischemia and poor neurological outcome. CSF GOT1 was significantly higher in patients with uncontrolled intracranial hypertension and cerebral ischemia post-SAH, and independently predicted poor neurological outcomes.

Background: Tumor heterogeneity poses major clinical challenges in high-grade gliomas (HGGs). Quantitative radiomic analysis with spatial tumor habitat clustering represents an innovative, noninvasive approach to represent and quantify tumor microenvironment heterogeneity. To date, habitat imaging has been applied mainly on conventional magnetic resonance imaging (MRI), although virtually extendible to any imaging modality, including advanced MRI techniques such as perfusion and diffusion MRI as well as PET imaging. Objectives: This study aims to evaluate an innovative PET and MRI approach for assessing hypoxia, perfusion, and tissue diffusion in HGGs and derive a combined map for clustering of intra-tumor heterogeneity. Methods: Seventeen patients harboring HGGs underwent a preoperative acquisition of MR perfusion (PWI), Diffusion (dMRI) and 18F-FAZA-PET imaging to evaluate tumor vascularization, cellularity, and hypoxia, respectively. Tumor volumes were segmented on FLAIR and T1 post-contrast images, and voxel-wise clustering of each quantitative imaging map identified eight combined PET and physiologic MRI habitats. Habitats’ spatial distribution, quantitative features and histopathological characteristics were analyzed. Results: A highly reproducible distribution pattern of the clusters was observed among different cases, particularly with respect to morphological landmarks as the necrotic core, contrast-enhancing vital tumor, and peritumoral infiltration and edema, providing valuable supplementary information to conventional imaging. A preliminary analysis, performed on stereotactic bioptic samples where exact intracranial coordinates were available, identified a reliable correlation between the expected microenvironment of the different spatial habitats and the actual histopathological features. A trend towards a higher representation of the most aggressive clusters in WHO grade IV compared to WHO III was observed. Conclusions: Preliminary findings demonstrated high reproducibility of the PET and MRI hypoxia, perfusion, and tissue diffusion spatial habitat maps and correlation with disease-specific histopathological features.