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Background and Aim: About a third of Pituitary Neuroendocrine Tumors (PitNETs) may show aggressive behavior. Many efforts have been performed for identifying possible predictive factors to early determine the future behavior of PitNETs. Programmed cell death ligand 1 (PD-L1) expression was associated with a more aggressive biology in different solid tumors, but its role in PitNET is not well-established yet. Our study aims to analyze PD-L1 expression in a surgical cohort of PitNETs to determine its association with radiological invasion and pathology findings, as well as with long-term recurrence rates., Methods: We performed a retrospective analysis in a series of 86 PitNETs. Clinical presentation and radiological features of the preoperative period were collected, as well as pathological data and follow-up data. The rate of PD-L1 expression was immunohistochemically evaluated and expressed as a tumor proportion score (TPS). We assessed its relationship with cavernous sinus invasion and Trouillas' classification as primary outcomes. Secondary outcomes included the TPS' relationship with histopathological markers of proliferation, hormonal expression, tumor size and long-term recurrence rates. We calculated the optimal cut-point for the primary outcomes while maximizing the product of the sensitivity and specificity and then we evaluated the significance of secondary outcomes with logistic regression analysis., Results: Eighty-six patients were included in the analysis; 50 cases were non-functional PitNETs. The TPS for PD-L1 showed a highly right-skewed distribution in our sample, as 30.2% of patients scored 0. Using Trouillas' classification, we found that "proliferative" cases have a significantly higher probability to express PD-L1 in more than 30% of tumor cells (OR: 5.78; CI 95%: 1.80-18.4). This same cut-point was also associated with p53 expression. A positive association was found between PD-L1 expression and GH expression ( p = 0.001; OR: 5.44; CI 95%: 1.98-14.98), while an inverse relationship was found with FSH/LH expression ( p = 0.014; OR = 0.27, CI 95%: 0.10-0.76). No association was found with CS invasion, tumor size, bone erosion or dura invasion. We could not find any association between PD-L1 expression and recurrence., Conclusions: PD-L1 expression was associated with proliferative grades of Trouillas' classification and p53 expression. We also confirmed a higher expression of PD-L1 in somatotroph tumors. Larger studies are necessary to investigate the relationship between PD-L1 expression and aggressive behaviors.

I n the context of an adequate health care organization, the figure of the neurologist as an emergency operator (in the emergency room-ER-and/or in a dedicated outpatient clinic) is crucial for an effective functional connection with the territory (and therefore with general practitioners), a reduction in inappropriate ER accesses, specific diagnostic and therapeutic approaches to neurological emergencies in the ER and a reduction in nonspecific or even unnecessary instrumental investigations. In this position paper of the Italian Association of Emergency Neurology (ANEU: Associazione Neurologia dell'Emergenza Urgenza), these issues are addressed, and two important organizational solutions are proposed: 1) The Neuro Fast Track, as an outpatient organization approach strongly linked to general practitioners and non-neurological specialists and dedicated to cases with deferrable urgency (to be assessed within 72 h) 2) The identification of an emergency neurologist, who is engaged in ER assessments as a consultant and involved in the management of the semi-intensive care unit of the emergency neurology and the stroke unit according to an appropriate rotation, as well as in consultations for patients with neurological emergencies in inpatient wards The possibility of computerizing the screening of patients with deferrable urgency in the Neuro Fast Track is described. A dedicated app represents an important tool that can facilitate the identification of patients for whom deferred assessment is appropriate, the scheduling of neurological examinations and reductions in the booking time through a more rapid approach to specialist assessment and subsequent investigations., (© 2023. Fondazione Società Italiana di Neurologia.)

This review aimed to compare the different responses of countries to the pandemic, their National Health Systems, and their impact on citizens' health. This work aimed to create a narrative plot that connects different discussion points and suggests organizational solutions and strategic choices in the face of the pandemic. In particular, this work focused on public health organizations, specifically the European Union and vaccination politics. It is also based on a case report series (about the United States, Germany, Vietnam, New Zealand, Cuba, and Italy), where each country has responded differently to the pandemic in terms of political decisions such as vaccination type, information to citizens, dealings with independent experts, and other specific country factors. In comparing the various models of care systems response to the pandemic, it emerges that: we have found some (few) good practices, but without global coordination, and this is obviously not enough. It is now quite clear that there cannot be a "good answer" in a single nation. Uncoordinated local responses cannot counter a global phenomenon. The second point is that the general context must be considered from a strategic point of view. With the threat of new pandemics (but also of health disasters linked to climate change, pollution, and wars), humanity finds itself at the crossroads between investing in a "democratic" management of international bodies but without power (and at the mercy of the need for funds with consequent conflicts) or in some new leadership proposals that advocate efficiency and problem-solving (and that would probably be able to implement it) but that would place processes totally outside of the public's control.

Abnormal deposition of α-synuclein is a key feature and biomarker of Parkinson's disease. α-Synuclein aggregates can propagate themselves by a prion-like seeding-based mechanism within and between tissues and are hypothesized to move between the intestine and brain. α-Synuclein RT-QuIC seed amplification assays have detected Parkinson's-associated α-synuclein in multiple biospecimens including post-mortem colon samples. Here we show intra vitam detection of seeds in duodenum biopsies from 22/23 Parkinson's patients, but not in 6 healthy controls by RT-QuICR. In contrast, no tau seeding activity was detected in any of the biopsies. Our seed amplifications provide evidence that the upper intestine contains a form(s) of α-synuclein with self-propagating activity. The diagnostic sensitivity and specificity for PD in this biopsy panel were 95.7% and 100% respectively. End-point dilution analysis indicated up to 106 SD50 seeding units per mg of tissue with positivity in two contemporaneous biopsies from individual patients suggesting widespread distribution within the superior and descending parts of duodenum. Our detection of α-synuclein seeding activity in duodenum biopsies of Parkinson's disease patients suggests not only that such analyses may be useful in ante-mortem diagnosis, but also that the duodenum may be a source or a destination for pathological, self-propagating α-synuclein assemblies., Competing Interests: BC, CDO and AH are inventors on patent applications pertaining to aSyn RT-QuIC technology. The other authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

This paper tries to summarize the results of studies from different disciplines supporting the idea that temperamental traits, such as "reckless/hyper-exploratory" attitudes, commonly believed to be associated with psychopathology, surprisingly turn out as adaptive under specific stress conditions. In particular, this paper analyzes an ethologic line of research on primates suggesting models for a sociobiological interpretation of mood disorders in humans; a study that found high frequencies of a genetic variance associated with bipolar disorder in people without bipolar disorder but with hyperactivity/novelty-seeking traits; the outcomes of socio-anthropologicalhistorical surveys on the evolution of mood disorders in Western countries in the last centuries; surveys on changing societies in Africa and African migrants in Sardinia; and studies that found higher frequencies of mania and subthreshold mania among Sardinian immigrants in Latin American megacities. Although it is not unequivocally accepted that an increase in the prevalence of mood disorders has occurred, it would be logical to suppose that a nonadaptive condition should have disappeared over time; mood disorders, on the contrary, persist and their prevalence might have even increased. This new interpretation could lead to counter-discrimination and stigma towards people suffering from the disorder, and it would be a central point in psychosocial treatments in addition to drugs. The aim is to hypothesize that bipolar disorder, strongly characterized by these traits, may be the result of the interaction between genetic characteristics, not necessarily pathological, and specific environmental conditions, rather than a mere product of an aberrant genetic profile. If mood disorders were mere nonadaptive conditions, they would have disappeared over time, however, their prevalence, paradoxically, persists if not even increases over time. The hypothesis that bipolar disorder may result from the interaction between genetic characteristics, not necessarily pathological, and specific environmental factors, seem more credible than considering bipolar disorder as a mere product of an aberrant genetic profile., Competing Interests: The authors report no conflicts of interest.

Advanced Therapy Medicinal Products (ATMPs) based on somatic cells expanded in vitro , with or without genetic modification, is a rapidly growing area of drug development, even more so following the marketing approval of several such products. ATMPs are produced according to Good Manufacturing Practice (GMP) in authorized laboratories. Potency assays are a fundamental aspect of the quality control of the end cell products and ideally could become useful biomarkers of efficacy in vivo . Here we summarize the state of the art with regard to potency assays used for the assessment of the quality of the major ATMPs used clinic settings. We also review the data available on biomarkers that may substitute more complex functional potency tests and predict the efficacy in vivo of these cell-based drugs., 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 Capelli, Cuofano, Pavoni, Frigerio, Lisini, Nava, Quaroni, Colombo, Galli, Bezukladova, Panina-Bordignon, Gaipa, Comoli, Cossu, Martino, Biondi, Introna and Golay.)

Background: To date, a few studies have systematically investigated differences in the clinical spectrum between acquired and idiopathic dystonias., Objectives: To compare demographic data and clinical features in patients with adult-onset acquired and idiopathic dystonias., Methods: Patients were identified from among those included in the Italian Dystonia Registry, a multicenter Italian dataset of patients with adult-onset dystonia. Study population included 116 patients with adult-onset acquired dystonia and 651 patients with isolated adult-onset idiopathic dystonia., Results: Comparison of acquired and idiopathic dystonia revealed differences in the body distribution of dystonia, with oromandibular dystonia, limb and trunk dystonia being more frequent in patients with acquired dystonia. The acquired dystonia group was also characterized by lower age at dystonia onset, greater tendency to spread, lower frequency of head tremor, sensory trick and eye symptoms, and similar frequency of neck pain associated with CD and family history of dystonia/tremor., Conclusions: The clinical phenomenology of dystonia may differ between acquired and idiopathic dystonia, particularly with regard to the body localization of dystonia and the tendency to spread. This dissimilarity raises the possibility of pathophysiological differences between etiologic categories., (© 2023 International Parkinson and Movement Disorder Society.)

Objective: The objective is to verify whether a genetic condition associated with bipolar disorder (BD) is frequent in old adults adapted to their environment, without BD, but with aptitudes for hyperactivity and novelty seeking (H/NS)., Methods: In this cross-sectional study, the study sample included healthy elderly people (40 participants, aged 60 or older) living in an urban area and recruited from a previous study on physical exercise and active aging, who were compared with 21 old adults with BD from the same area. The genetic methodology consisted of blood sampling, DNA extraction, real-time PCR jointly with FRET probes, and the SANGER sequencing method. The genetic variant RS1006737 of CACNA1C, found to be associated with bipolar disorder diagnosis, was investigated., Results: The frequency of the RS1006737 genetic variant in the study group (H/NS) is not higher than in the BD group and is statistically significantly higher than in all the control groups found in the literature. However, the familiarity for BD is higher in old adults with BD than in the H/NS sample without BD. The risk of BD in the family (also considering those without BD but with family members with BD) is not associated with the presence of the genetic variant examined., Conclusion: The study suggests that the gene examined is associated with characteristics of hyperactivity rather than just BD. Nevertheless, choosing to participate in an exercise program is an excessively general way to identify H/NS. The next step would be to identify the old adults with well-defined H/NS features with an adequate tool., Competing Interests: Dr. Antonio Nardi is on the Editorial Advisory Board of the journal Clin Pract Epidemiol Ment Health., (© 2023 Kalcev et al.)

Objective: This paper illustrates the preliminary psychometric properties of the Questionnaire for Adaptive Hyperactivity and Goal Achievement (AHGA), aimed at measuring adaptive characteristics of hyperactivity and goal pursuit in older adults., Methods: The 12-item scale was administered to a sample of 120 subjects (older adults) between February 2022 and June 2022. The reliability of AHGA was measured using Cronbach's alpha, and factor structure was established using parallel analysis (PA) and principal component analysis (PCA). Convergent validity was tested against the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN)., Results: All included subjects have an average age of 74.1±5.1 years. AHGA reliability was good (Cronbach's alpha: 0.713 [95%CI: 0.630 to 0.783]). Factor analysis suggested two main components: goal achievement and hyperactivity, which explained 41% of the variance in the data. The results support the convergent validity of the scale: AHGA measures adaptive characteristics of hyperactivity and goal pursuit, in contrast to BRIAN, which measures pathological characteristics., Conclusion: The reported findings represent an innovative approach to hyperthymic features by embracing a broader spectrum concept that conceptualizes the potential transition between pathological and adaptive aspects as a continuum., Competing Interests: The authors declare no conflicts of interest, financial or otherwise., (© 2023 Kalcev et al.)

Background: The role of domain-general cognitive abilities in the etiology of Developmental Dyscalculia (DD) is a hotly debated issue., Aims: In the present study, we tested whether WISC-IV cognitive profiles can be useful to single out DD., Methods and Procedures: Using a stringent 2-SD cutoff in a standardized numeracy battery, we identified children with DD (N = 43) within a clinical sample referred for assessment of learning disability and compared them in terms of WISC cognitive indexes to the remaining children without DD (N = 100) employing cross-validated logistic regression., Outcomes and Results: Both groups showed higher Verbal Comprehension and Perceptual Reasoning than Working Memory and Processing Speed, and DD scores were generally lower. Predictive accuracy of WISC indexes in identifying DD individuals was low (AUC = 0.67) and it dropped to chance level in discriminating DD from selected controls (N = 43) with average math performance but matched on global IQ. The inclusion of a visuospatial memory score as an additional predictor did not improve classification accuracy., Conclusions and Implications: These results demonstrate that cognitive profiles do not reliably discriminate DD from non-DD children, thereby weakening the appeal of domain-general accounts., Competing Interests: Conflict of Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Central nervous system tumors are the most common solid neoplasm in children, 60%-70% occurring in the posterior fossa. Surgery is the mainstay of treatment but surgery in the pediatric population is associated with a high risk of perioperative complications. We aimed at analyzing the perioperative complications after posterior fossa surgery in a pediatric population and identifying the associated risk factors., Methods: Retrospective study of all pediatric patients undergoing surgery for resection of a posterior fossa tumor between 1999 and 2019, at the University Hospital of Lausanne. Data were collected including age, clinical presentation, tumor localization, presence of preoperative hydrocephalus, timing of surgery, surgical approach, surgical team, extent of surgical resection, perisurgical complications, and histopathological diagnosis. Statistical analysis was performed to correlate the data with the risk of complications., Results: Sixty-seven patients were included. Perisurgical complications were identified in 39 patients (58.2%), of which 14 (35.9%) required corrective interventions. The perioperative mortality rate was zero. In the univariate analysis, surgery performed under emergency conditions, transvermian and telovelar approaches were statistically correlated with an increased rate of complications. Extent of resection, hydrocephalus, and Lansky index at presentation were not predictive of perioperative complications. Midline tumor, tumor volume >25 cm 3 , and surgery performed by a nonspecialized pediatric onconeurosurgeon were found to be independent risk factors in the multivariate analysis., Conclusions: Surgery in the posterior fossa in the pediatric population harbors a high risk of complications. Identifying the variables contributing to these complications is important in order to improve surgical management of these patients., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Under certain conditions, the hyperthymic temperament traits associated with an increased risk of developing bipolar disorders may in fact produce adaptive responses. The purpose of this study is to see if the type of biological material used for genetic analysis (saliva or blood) affects the detection of mutations in the CACNA1C (RS1006737) gene. The first experimental group consisted of Sardinian migrants ("volunteers") in South American and European megacities. The second experimental group consisted of older healthy subjects with hyperactivity and novelty-seeking characteristics from Cagliari, Italy. The genetic procedure included DNA extraction, real-time PCR, and the Sanger method. Nonetheless, the authors believe that saliva is the most appropriate biological material, given its many advantages. In contrast to blood, saliva can be collected by any type of healthcare provider after following a few simple instructions., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Cognitive impairment is a frequent consequence of bipolar disorder (BD) that is difficult to prevent and treat. In addition, the quality of the preliminary evidence on the treatment of BD through Cognitive Remediation (CR) with traditional methods is poor. This study aims to evaluate the feasibility of a CR intervention with fully immersive Virtual Reality (VR) as an additional treatment for BD and offers preliminary data on its efficacy., Methods: Feasibility randomized controlled cross-over clinical study, with experimental condition lasting three months, crossed between two groups. Experimental condition: CR fully immersive VR recovery-oriented program plus conventional care; Control condition: conventional care. The control group began the experimental condition after a three months period of conventional care (waiting list). After the randomization of 50 people with BD diagnosis, the final sample consists of 39 participants in the experimental condition and 25 in the control condition because of dropouts., Results: Acceptability and tolerability of the intervention were good. Compared to the waitlist group, the experimental group reported a significant improvement regarding cognitive functions (memory: p = 0.003; attention: p = 0.002, verbal fluency: p = 0.010, executive function: p = 0.003), depressive symptoms ( p = 0.030), emotional awareness ( p = 0.007) and biological rhythms ( p = 0.029)., Conclusions: The results are preliminary and cannot be considered exhaustive due to the small sample size. However, the evidence of efficacy, together with the good acceptability of the intervention, is of interest. These results suggest the need to conduct studies with larger samples that can confirm this data., Trial Registration: ClinicalTrialsgov NCT05070065, registered in September 2021.

Refractory subhemispheric epilepsy has been traditionally treated by resection. The last few decades have seen the emergence of disconnective techniques, for both hemispheric and subhemispheric disease. The aim of this study was to describe the technique for a disconnective surgery for large epileptogenic lesions involving the central (perirolandic cortices), parietal, and occipital lobes. This junctional cortex within the hemisphere (in contrast to anterior and posterior quadrantotomies) presents unique challenges when contemplating a complete disconnection of the region. The surgical technique is achieved through six distinct steps: fronto-central, inferior frontoparietal, lateral temporo-occipital, medial frontal, basal temporo-occipital, and posterior parasagittal callosal disconnections. The functional neuroanatomy of each step is described, along with cadaveric dissections. The authors describe this technique and include a case description of a young girl who presented with childhood-onset intractable epilepsy associated with cognitive stagnation. The postoperative seizure outcome in this patient remains excellent at 2 years' follow-up, with gains in cognition and behavior. Excellent seizure outcomes can be achieved if the network encompassing the entire epileptogenic cortex is disconnected while ensuring preservation of fiber systems that link functionally eloquent uninvolved cortices adjacent to the central quadrant.

Advanced gene and cellular therapies risk a second "valley of death" due to their high costs and low patient population. As these are life-saving therapies, measures are urgently needed to prevent their withdrawal from the market., (© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

This work is part of a research project that aims to measure organisational well-being, human rights respect and quality of care in mental health services in Sardinia, Italy, country that has replaced long-stay psychiatric hospitals with community mental health services. Previous contributions have seen Italian health professionals and users as the most satisfied and optimistic about the quality of the mental health care provided and the respect they offer for service users' rights. Our aim is to confirm these findings by comparing experiences of users of mental health services with those of other care services in the same region. Our findings indicate that mental health services users show higher level of satisfaction for care and higher perception of users' human rights respect compared to non-mental health facilities users. They also have greater satisfaction with organisational aspects of services and they are more convinced that the health professionals rights are respected. In contrast, they are less satisfied with the resources available for care centres than other users and require more professional psychosocial support. We want to allow future comparisons to other regions on quality assessment through the perception of users and worker on respect for standards and human rights.

Introduction: Involuntary hospitalisation denies autonomy and freedom of decision-making and is frequent in psychiatric clinical practice. However, there is still a lack of knowledge of long-term compliance after Involuntary commitment., Methods: We conducted a systematic review of published studies reporting people compliance after involuntary hospitalisation and people compliance after voluntary admission. Two investigators independently searched PubMed, PsycINFO, EMBASE and CINAHL up to December 17th, 2021 to identify eligible studies. The study is registered with PROSPERO number CRD42022299437., Results: Ten independent studies analysing the main indicators of compliance, engagement with services and medication adherence, were included. Three studies show that compliance is worse in people that have been involuntary hospitalised and in the others no association is found. Just two of the ten studies show an association with improved compliance. Outcomes are assessed from the first follow-up appointment after discharge up to 96 months., Conclusions: Although evidences carried out so far are weak, the data do not show a trend of improvements and do not seem to exclude the possibility of worse compliance after compulsory hospitalisation. More appropriate methodologies and reliable assessment are needed in future research to provide scientific evidence on involuntary admission health effects.

In 2002 we published an article describing a population of vessel-associated progenitors that we termed mesoangioblasts (MABs). During the past decade evidence had accumulated that during muscle development and regeneration things may be more complex than a simple sequence of binary choices (e.g., dorsal vs. ventral somite). LacZ expressing fibroblasts could fuse with unlabelled myoblasts but not among themselves or with other cell types. Bone marrow derived, circulating progenitors were able to participate in muscle regeneration, though in very small percentage. Searching for the embryonic origin of these progenitors, we identified them as originating at least in part from the embryonic aorta and, at later stages, from the microvasculature of skeletal muscle. While continuing to investigate origin and fate of MABs, the fact that they could be expanded in vitro (also from human muscle) and cross the vessel wall, suggested a protocol for the cell therapy of muscular dystrophies. We tested this protocol in mice and dogs before proceeding to the first clinical trial on Duchenne Muscular Dystrophy patients that showed safety but minimal efficacy. In the last years, we have worked to overcome the problem of low engraftment and tried to understand their role as auxiliary myogenic progenitors during development and regeneration., Competing Interests: MC is employed by Lunapore. GG and HH by Cell Fiber.Co. GR by Roche and UR by Gupra. The remaining 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. The reviewer (KV) declared a shared parent affiliation with the author(s) (MQ) to the handling editor at the time of review., (Copyright © 2023 Cossu, Tonlorenzi, Brunelli, Sampaolesi, Messina, Azzoni, Benedetti, Biressi, Bonfanti, Bragg, Camps, Cappellari, Cassano, Ciceri, Coletta, Covarello, Crippa, Cusella-De Angelis, De Angelis, Dellavalle, Diaz-Manera, Galli, Galli, Gargioli, Gerli, Giacomazzi, Galvez, Hoshiya, Guttinger, Innocenzi, Minasi, Perani, Previtali, Quattrocelli, Ragazzi, Roostalu, Rossi, Scardigli, Sirabella, Tedesco, Torrente and Ugarte.)

Background: Hydrocephalus is one of the major complications of aneurysmal subarachnoid haemorrhage (aSAH). In the acute setting, an external ventricular drain (EVD) is used for early management. A cisternal drain (CD) coupled with the micro-surgical opening of basal cisterns can be an alternative when the aneurysm is clipped. Chronic hydrocephalus after aSAH is managed with ventriculo-peritoneal (VP) shunt, a procedure associated with a wide range of complications. The aim of this study is to analyse the impact of micro-surgical opening of basal cisterns coupled with CD on the incidence of VP shunt, compared to patients treated with EVD., Methods: The authors conducted a retrospective review of 89 consecutive cases of patients with aSAH treated surgically and endovascularly with either EVD or CD between January 2009 and September 2021. Patients were stratified into two groups: Group 1 included patients with EVD, Group 2 included patients with CD. Subgroup analysis with only patients treated surgically was also performed. We compared their baseline characteristics, clinical outcomes and shunting rates., Results: There were no statistically significant differences between the two groups in terms of epidemiological characteristics, WFNS score, Fisher scale, presence of intraventricular hemorrhage (IVH), acute hydrocephalus, postoperative meningitis or of clinical outcomes at last follow-up. Cisternostomy with CD (Group 2) was associated with a statistically significant reduction in VP-shunt compared with the use of an EVD (Group 1) (9.09% vs 53.78%; p < 0.001). This finding was confirmed in our subgroup analysis, as among patients with a surgical clipping, the rate of VP shunt was 43.7% for the EVD group and 9.5% for the CD group (p = 0.02)., Conclusions: Cisternostomy with CD may reduce the rate of shunt-dependent hydrocephalus. Cisternostomy allows the removal of subarachnoid blood, thereby reducing arachnoid inflammation and fibrosis. CD may enhance this effect, thus resulting in lower rates of chronic hydrocephalus., (© 2022. The Author(s).)

Objective: Aesthetic assessment after surgery for non-syndromic single suture craniosynostosis (SSC) is crucial. Surgeons' evaluation is generally based on Whitaker classification, while parental impression is generally neglected. The aim of this paper is to compare aesthetic perceptions of parents and surgeons after surgery for SSC, expressed by a 10-item questionnaire that complement Whitaker's classification., Methods: The authors submitted a 10-item questionnaire integrating Whitaker's classification in order to evaluate the degree of satisfaction, the detailed aesthetics results and the need for surgical revision, to surgeons and parents of a consecutive series of patients operated for SSC between January 2007 and December 2018. The results were collected blindly., Results: A total of 70 patients were included in the study. Scaphocephaly and trigonocephaly were the two most frequent craniosynostosis. Parents and surgeons general aesthetics evaluation and average rating for Whitaker's classification were 1.86 vs 1.67 (p = 0.69) and 1.19 vs 1.1 (p = 0.45) respectively. Parents' evaluation for scar perception and alopecia (p < 0.00001), the presence of bony crest (0.002), bony bump (p < 0.00001), or other bone irregularities (p = 0.02) are significantly worse when compared to surgeons' perception., Conclusions: Parents seem to be more sensitive to the detection of some aesthetic anomalies and their opinion should not be neglected. The authors propose a modified Whitaker classification based on their results to better stratify the aesthetic outcome after surgery for SSC., (© 2022. The Author(s).)

A long-standing debate concerns whether developmental dyscalculia is characterized by core deficits in processing nonsymbolic or symbolic numerical information as well as the role of domain-general difficulties. Heterogeneity in recruitment and diagnostic criteria make it difficult to disentangle this issue. Here, we selected children ( n = 58) with severely compromised mathematical skills (2 SD below average) but average domain-general skills from a large sample referred for clinical assessment of learning disabilities. From the same sample, we selected a control group of children ( n = 42) matched for IQ, age, and visuospatial memory but with average mathematical skills. Children with dyscalculia showed deficits in both symbolic and nonsymbolic number sense assessed with simple computerized tasks. Performance in the digit-comparison task and the numerosity match-to-sample task reliably separated children with developmental dyscalculia from controls in cross-validated logistic regression (area under the curve = .84). These results support a number-sense-deficit theory and highlight basic numerical abilities that could be targeted for early identification of at-risk children as well as for intervention.

It is hypothesized that factors associated with bipolar disorder could, uer defined conditions, produce adaptive behaviors. The aim is to verify whether a genetic feature associated with bipolar disorder can be found in people without bipolar disorder but with hyperactivity/exploration traits. Healthy old adults (N = 40) recruited for a previous study on exercise were subdivided using a previously validated tool into those with and without hyperactivity/exploration traits and compared with a group of old patients with bipolar disorder (N = 21). The genetic variant RS1006737 of CACNA1C was analyzed using blood samples, DNA extraction, real-time PCR, FRET probes, and SANGER method sequencing. People with hyperactivity/exploration traits and without bipolar disorder were like people with bipolar disorder regarding the frequency of the genetic variant (OR = 0.79, CI95%: 0.21-2.95), but were different from people without either hyperactivity/exploration traits and bipolar disorder (OR = 4.75, CI95%: 1.19-18.91). The combined group of people with hyperactivity/exploration traits without bipolar disorder plus people with bipolar disorder had a higher frequency of the variant than people without either hyperactivity/exploration traits or bipolar disorder (OR = 4.25, CI95%: 1.24-14.4). To consider the genetic profile of bipolar disorder not an aberrant condition opens the way to a new approach in which the adaptive potential would be a central point in psychosocial treatment in addition to drug therapy. Future research can confirm the results of our study.

Background: Recently in the field neurodegenerative diseases increasing attention has been pointed to CSF biomarkers and their integration with neuroimaging (1). Frontotemporal lobar degeneration (FTLD) refers to a heterogeneous group of clinical syndromes with different underlying proteinopathies including tau pathology. CSF biomarkers have been proposed as diagnostic and prognostic factors. Aim of our study was to evaluate the relationship between CSF tau biomarkers and structural MRI brain measures in FTLD., Methods: We included early FTLD patient. All included patients underwent lumbar puncture to evaluate amyloid, total-tau (t-tau), phospho-tau 181 (p-tau); p-tau/t-tau ratio was also calculated; brain MRI was performed to estimate whole brain volume, volume of principal deep grey matter structures and regional cortical thickness., Results: Demographic characteristics of the 28 included patients were as follows: female/male: 9/19; mean ± SD age: 68.1 ± 7.8 years. The p-tau/t-tau ratio was significantly correlated with whole brain volume (r = 0.69; p: 0.001), left putamen volume (r = 0.55 p: 0.009), left pallidum volume (r = 0.41; p: 0.01), right accumbens area (r = 0.47; p: 0.02). P-tau/t tau ratio showed also a significant correlation with cortical thickness of left temporal lobe (r = 0.74; p: 0.001) and right lateral orbital frontal cortex (r = 0.45; p: 0.03). Linear regression showed a significant relationship between p-tau/t-tau ratio and left temporal pole (p = 0.01; r 2 : 0.60) and brain volume (p:0.002; r 2 : 0.56) after controlling for age and gender., Conclusions: Our data suggest that CSF biomarkers, especially p-tau/t-tau ratio, could play a role as prognostic factor in FTLD. Further longitudinal investigations are needed to confirm these findings., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest regarding this research., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The combined petrosal approach is an excellent method to access the petroclival region but has the inherent risk of injury to the temporal lobe and Vein of Labbé. Tentorial peeling has the potential to largely eliminate these risks during the classic combined transpetrosal approach., Methods: Anatomical dissection of three adult injected non-formalin fixed cadaveric heads was performed. Combined petrosal approach with tentorial peeling was completed. A tentorial incision just superior and parallel to the superior petrosal sinus was made to enable peeling of the tentorium into two layers, the posterior fossa tentorial leaf (PFTL), and the temporal tentorial leaf (TTL)., Results: Tentorial peeling clearly exposed the continuity between the temporal dura and the TTL as well as the continuity between the presigmoid dura and the PFTL. This enabled the creation of a large dural flap extending to the tentorial incisura, providing wide access to the petroclival region without any exposure of the temporal lobe and/or basal temporal veins. Techniques to create the dural flap without trochlear nerve injury were also explored., Conclusion: The technique of tentorial peeling into two distinct layers has the potential to reduce the morbidity associated with temporal lobe retraction and venous injury. Further cadaveric studies and surgical case series are needed to validate this important surgical nuance in transpetrosal approaches., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

KMT2B-related dystonia (DYT-KMT2B, also known as DYT28) is an autosomal dominant neurological disorder characterized by varying combinations of generalized dystonia, psychomotor developmental delay, mild-to-moderate intellectual disability and short stature. Disease onset occurs typically before 10 years of age. We report the clinical and genetic findings of a series of subjects affected by adult-onset dystonia, hearing loss or intellectual disability carrying rare heterozygous KMT2B variants. Twelve cases from five unrelated families carrying four rare KMT2B missense variants predicted to impact protein function are described. Seven affected subjects presented with adult-onset focal or segmental dystonia, three developed isolated progressive hearing loss, and one displayed intellectual disability and short stature. Genome-wide DNA methylation profiling allowed to discriminate these adult-onset dystonia cases from controls and early-onset DYT-KMT2B patients. These findings document the relevance of KMT2B variants as a potential genetic determinant of adult-onset dystonia and prompt to further characterize KMT2B carriers investigating non-dystonic features., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Prdm1 mutant mice are one of the rare mutant strains that do not develop whisker hair follicles while still displaying a pelage. Here, we show that Prdm1 is expressed at the earliest stage of whisker development in clusters of mesenchymal cells before placode formation. Its conditional knockout in the murine soma leads to the loss of expression of Bmp2 , Shh , Bmp4 , Krt17 , Edar , and Gli1 , though leaving the β-catenin-driven first dermal signal intact. Furthermore, we show that Prdm1 expressing cells not only act as a signaling center but also as a multipotent progenitor population contributing to the several lineages of the adult whisker. We confirm by genetic ablation experiments that the absence of macro vibrissae reverberates on the organization of nerve wiring in the mystacial pads and leads to the reorganization of the barrel cortex. We demonstrate that Lef1 acts upstream of Prdm1 and identify a primate-specific deletion of a Lef1 enhancer named Leaf. This loss may have been significant in the evolutionary process, leading to the progressive defunctionalization and disappearance of vibrissae in primates.

Introduction: Cognitive deficits are considered a fundamental component of bipolar disorder due to the fact that they negatively impact personal/social functioning. Cognitive remediation interventions are effective in the treatment of various psychosocial disorders, including bipolar disorder. The use of Virtual reality as a rehabilitation tool has produced scientific evidence in recent years, especially in cardiovascular, neurological, and musculoskeletal rehabilitation. This study aims at evaluating the feasibility of a Cognitive Remediation Virtual Reality Program (CEREBRUM) for people with bipolar disorder in psychiatric rehabilitation., Material and Methods: Feasibility randomized controlled cross-over clinical study; we randomized 50 people from the Consultation and Psychosomatic Psychiatry Center of the University Hospital of Cagliari (San Giovanni di Dio Civil Hospital) with a diagnosis of bipolar disorder. We propose a cognitive remediation program in virtual reality (CEREBRUM), 3 months with 2 weekly sessions, for the experimental group and a usual care program for the control group (psychiatric visit and/or psychotherapy)., Results: The results of the trial will be published in international peer-reviewed journals and will be disseminated at international meetings and congress., Discussion: This RCT aims, with regards to its feasibility and design, to provide information about a confirmatory trial that evaluates the effectiveness of a Virtual Reality Cognitive Remediation program in psychiatric rehabilitation for the treatment of cognitive dysfunction in people with bipolar disorder., Conclusion: The results that we analyzed at the end of the RCT will have an impact on psychiatric rehabilitation research with a focus on improving the application of technologies for mental health.Trial registration: ClinicalTrialsgov NCT05070065, registered on September 2021., Competing Interests: The authors declare no conflict of interest, financial or otherwise. Two co-authors (VDL and LDN) are the legal administrators of the societies that have developed CEREBRUM software., (© 2022 Perra et al.)

Background: Cerebrospinal fluid tap test is a common procedure to predict the efficacy of ventriculoperitoneal shunt for idiopathic normal pressure hydrocephalus. Objective tests after cerebrospinal fluid tap test are used to establish the surgical indication, but subjective improvements may also be important in selection of surgical candidates. The aim of this study was to evaluate surgical outcomes of patients with ventriculoperitoneal shunt for idiopathic normal pressure hydrocephalus, comparing patients showing objective improvement with patients improving only on subjective assessments., Methods: In this retrospective analysis, patients were divided into 2 groups: group 1 included patients with improvement on objective evaluation after cerebrospinal fluid tap test; group 2 included patients who showed only subjective improvement. The surgical outcomes of the 2 groups were compared., Results: Of 28 included patients, 17 were objective responders (group 1), and 11 were subjective responders (group 2). Clinical and radiological characteristics were similar. The only significant difference was the baseline Berg Balance Scale, which was lower in objective responders (P = 0.0015). At 3 months after surgery and at last follow-up, there was no difference in surgical outcomes between the 2 groups. However, in the group of subjective responders, a continuous improvement for incontinence and gait was more frequently observed (P = 0.04 and P < 0.001, respectively)., Conclusions: Surgical outcomes after ventriculoperitoneal shunt were similar between the 2 groups, with a more favorable trend in terms of symptom improvement for subjective responders. Subjective assessment seems to be an important factor to consider in preoperative evaluation., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: During the Covid-19 pandemic, delays in providing medical services, dissatisfaction, criticism toward health workers (HW) and the risk of burnout of HW in Italy have been documented. No studies have contrasted the point of view of HW and users on the quality of care and respect for human rights in health facilities., Objective: To compare the perception of users of their satisfaction with the care provided with the perception of HW of their satisfaction with work as well as the perception of the respect of HW "s and users" human rights., Methods: The "Well-Being at work and respect for human rights questionnaire" (WWRR) was administered on a sample of users (142) and HW (154) in four outpatient health care facilities of a hospital in Sardinia, Italy., Results: Users showed higher scores than HW on their satisfaction with the care received ( p  < 0.0001), the perception of respect for their human rights ( p  < 0.0001), and availability of resources for care ( p  < 0.0001). The HW scores were higher than 50% of the maximum in all items, but a relatively low score was reported on the HW's satisfaction of the resources and the respect for their rights., Conclusion: The satisfaction for care and respect for human rights in the outpatient health services was higher than expected. The relatively low score by the HWs in relation to the satisfaction with the resources and perception of respect for their human rights could be a wake-up call. The study does not involve emergency rooms, wards, or Covid units., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

To verify if lethality and diffusivity of Covid-19 correlated with percentage of people vaccinated in different countries and whether results on these indicators were comparable under different types of vaccines. A linear regression analysis was conducted between vaccines/inhabitant, new cases/inhabitants and ratio deaths/cases. A comparison between the three indicators was carried out in countries subdivided by kind of vaccine. The proportion of vaccinations/inhabitants correlates negatively with proportion of deaths × 100 cases ( R  = -3.90, p  < 0.0001), but didn't on incidence of new cases. Countries with prevalence of mRNA vaccines were similar to others on incidence of new cases; but a lower lethality of Sars-Cov2 was found than in countries with prevalence of viral vehicle vaccines ( F  = 6.064, p  = 0.0174) but didn't against countries with prevalence of inactivated vaccines. The higher is the proportion of vaccine/inhabitant in a given country, the less is the fraction of infected people who die., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Falcotentorial meningiomas are rare tumors that arise at the junction of the dural folds of the tentorium and falx cerebri, at the junction of the vein of Galen with the straight sinus with possible extensions along the course of the straight sinus. Surgery of falcotentorial meningiomas remains challenging due to the intimate neurovascular relationships in the posterior incisural space., Methods: We describe the key steps of the occipito-transtentorial approach for falcotentorial meningiomas with a video illustration. The surgical anatomy is described along with the advantages and limitations of this approach., Conclusion: The occipito-transtentorial approach offers good surgical exposure and outcomes in carefully selected patients harboring falcotentorial meningiomas. Precise understanding of the relationship between the tumor and the internal cerebral veins, basal veins, and vein of Galen should be thoroughly analyzed as these structures may be infiltrated or displaced., (© 2022. The Author(s).)

Lomustine (1-[2-chloroethyl]3-cyclohexyl-1-nitrosurea, CCNU) is an oral alkylating agent in the nitrosourea subclass that can cause myelosuppression, with neutropenia being the main dose-limiting toxicity. The aim of this study was to define the frequency of neutropenic events and to identify predisposing risk factors in tumour-bearing dogs treated with CCNU. Dogs receiving CCNU for various malignancies were identified following a search of hospital databases. Variables analysed for correlation with neutropenia included signalment, body weight, tumour type, CCNU total dose, steroid use, protocol type, use of L-asparaginase, previous anthracycline administration and use of the drug as first-line or in the rescue setting. One-hundred and fifteen cases were included; median age was 7 years (range 1-14 years) and median body weight 27.6 kg (range 3-74 kg). The median CCNU dose was 63.5 mg/m 2 (range 27.7-84.9 mg/m 2 ). Neutropenia occurred in 75 cases (65%) and was comprised of grade 1 (28%), 2 (16%), 3 (29.3%) and 4 (26.7%) events. Tumour type (histiocytic sarcoma [HS]), use of CCNU first line, dose >70 mg/m 2 , absence of co-morbidities and previous anthracycline administration, were significantly associated with an increased risk of developing neutropenia, including high-grade events. There was a 1.7% reported mortality rate. When CCNU is used in dogs with HS, first-line, at a starting dosage >70 mg/m 2 , in patients with no co-morbidities or with a history of previous anthracycline administration, there may be an increased risk of developing neutropenia. These data may help guide treatment decisions and minimize treatment delays or potentially life-threatening complications., (© 2022 John Wiley & Sons Ltd.)

Objective: Large and giant pituitary adenomas (L- and G-PAs) continue to remain a surgical challenge. The diaphragm may have a role in determining the shape of the tumor and therefore influencing the extent of resection. Our study aims to analyze our surgical series of L- and G-PAs according to their relationship with the diaphragm and invasion of cavernous sinus (CS)., Material and Methods: We performed a retrospective analysis of our surgical series of patients operated for L- and G-PAs. We categorized the tumors into four grades according to their relationship with the diaphragm: grade 1 (supradiaphragmatic component with a wide incompetent diaphragm), grade 2 (purely infra-diaphragmatic tumor with a competent diaphragm), grade 3 (dumbbell-shape tumors), and grade 4 (multilobulated tumor with invasion of the subarachnoid space)., Results: A total of 37 patients were included in our analysis. According to our classification, 43.3% of patients had grade 1 tumors, 27% had grade 2, 5.4% had grade 3, and 24.3% had grade 4 tumors. CS invasion was confirmed intraoperatively in 17 out of 37 patients (46%). The gross total resection (GTR) was obtained in 19% of the cases, near-total resection in 46%, and subtotal resection in 35%. All the patients who achieved GTR had grade 1 tumors and the lowest rate of CS invasion ( p  < 0.01)., Conclusion: Radiological evaluation of the tumor relationship with the diaphragm, invasion of CS, and invasion of the subarachnoid space are crucial to plan the surgical strategy and maximize the possibilities of achieving GTR in L- and G-PAs., 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., (© 2022 Harel, Cossu, Daniel and Messerer.)

Background: The relationship between toxoplasma gondii (T. gondii) infection and bipolar disorder (BD) is poorly understood. This review explores this relationship by estimating the strength of the association between the two conditions using data from published studies., Methods: Following PRISMA guidelines, we performed a review and meta-analysis of published articles obtained from a systematic search of PubMed, PsycINFO, EMBASE and the Cochrane library up to January 10th, 2021. We included observational studies that compared seroprevalence of IgG class antibodies against T. gondii in patients with a diagnosis of BD with healthy controls. We excluded studies that included <10 participants in each study arm and patients with a serious concomitant medical illness. Discrepancies between the two independent researchers were resolved by consulting a third experienced researcher. Summary data were extracted from published reports. Analysis was conducted using both fixed-effects and random-effects models. The study is registered with PROSPERO number CRD42021237809., Findings: The search yielded 23 independent studies with a total of 12690 participants (4021 with BD and 8669 controls). Persons with BD had a greater odd of seropositivity with toxoplasmosis than controls, both in the fixed-effects model (OR = 1.34 [95%CI: 1.19 to 1.51]) and the random-effects model (OR = 1.69 [95%CI: 1.21 to 2.36]). No publication bias was detected but reported results showed a high heterogeneity (I2 = 84% [95%CI:77%-89%])., Interpretation: The findings support the relationship between toxoplasmosis infection and BD and suggests a need for studies designed to explore possible causal relationship. Such studies may also improve our understanding of the pathophysiology of BD and open other avenues for its treatment., Funding: P.O.R. Sardegna F.S.E. 2014-2020., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Physical exercise has been shown to improve dysmetabolism in older adults, reducing cardiovascular risk, while its role in preventing dysmetabolism is less known. Moreover, most of the trials use exercise programs that are difficult to put into daily practice. The purpose of this Randomized Controlled Trial (RCT) was to evaluate the effectiveness of a 3-month moderate exercise program in improving or preventing dysmetabolism in 120 older adults, randomly selected for the exercise program (experimental group) or cultural activities (control group). None of the subjects were following a hypocaloric diet, and all of them reported healthy eating habits. Anthropometric (Body Mass Index (BMI) and Waist Circumference (WC)) and metabolic variables (fasting plasma glucose (FPG), High-Density Lipoprotein Cholesterol (HDL-C), and triglycerides (TG)) were assessed at baseline (T0) and at the end of the trial (T1). Dysmetabolism was defined by the presence of an increased WC plus at least two metabolic alterations. At T0, the two groups did not differ by sex, age, education, BMI, WC, FPG, HDL-C levels, and prevalence of dysmetabolism. The mean BMI value indicated overweight, and WC values were higher than the cut-off. At T1, a slight reduction in the number of people with dysmetabolism was found only in the experimental group. However, none of the individuals without dysmetabolism at T0 in the experimental group developed it at T1, while 11.4% developed it in the control group ( p = 0.032). This study highlights that a moderate exercise program, accessible in daily practice, can prevent dysmetabolism in older adults, even while being overweight, while if dysmetabolism is already present, more prolonged combined nutritional and exercise interventions will be needed.

Introduction: Pituitary apoplexy (PA) is a rare, and potentially life-threatening condition, caused by hemorrhage or infarction into the pituitary gland with a rapid expansion of the contents of the sella turcica, associated with sudden intense headache, neurological and endocrinological deterioration. The identification of risk factors is crucial for prevention and optimal management. Herein we report a case of PA occurring 1 month after the initiation of anabolic androgenic steroid abuse for bodybuilding., Case Report: A 40-year-old male patient presents with abrupt onset headache associated with left partial third cranial nerve palsy. The MRI shows a sellar lesion involving left cavernous sinus with a heterogenous anterior aspect of the lesion with hemorrhagic zones in favor of PA. Endocrine work-up shows high testosterone level in patient who was using exogenous testosterone without a medical prescription for a month., Conclusion: We report a case of PA of a pituitary neuroendocrine tumor occurring shortly after AAS. The association between PA and AAS should be considered as a potential risk., 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 © 2022 Andriuskeviciute, Cossu, Ameti, Papadakis, Daniel, Dunet and Messerer.)

Objective: Cochlear nerve preservation during surgery for vestibular schwannoma (VS) may be challenging. Brainstem auditory evoked potentials and cochlear compound nerve action potentials have clearly shown their limitations in surgeries for large VSs. In this paper, the authors report their preliminary results after direct electrical intraoperative cochlear nerve stimulation and recording of the postauricular muscle response (PAMR) during resection of large VSs., Methods: The details for the electrode setup, stimulation, and recording parameters are provided. Data of patients for whom PAMR was recorded during surgery were prospectively collected and analyzed., Results: PAMRs were recorded in all patients at the ipsilateral vertex-earlobe scalp electrode, and in 90% of the patients they were also observed in the contralateral electrode. The optimal stimulation intensity was found to be 1 mA at 1 Hz, with a good cochlear response and an absent response from other nerves. At that intensity, the ipsilateral cochlear response had an initial peak at a mean (± SEM) latency of 11.6 ± 1.5 msec with an average amplitude of 14.4 ± 5.4 µV. One patient experienced a significant improvement in his audition, while that of the other patients remained stable., Conclusions: PAMR monitoring may be useful in mapping the position and trajectory of the cochlear nerve to enable hearing preservation during surgery.

Background: Since 2011 Italy has faced an extraordinary increase in migrants arrivals, mainly from the Mediterranean route, one of the world's most dangerous journeys. The purpose of the present article is to provide a comprehensive picture of the migrants' health status in the "T. Fenoglio" centre, Settimo Torinese (Turin, Italy)., Methods: A retrospective cross-sectional study was conducted using data collected from June 2016 to May 2018 on adult migrants (over 18 years old) from Africa, Middle East and South East Asia (Bangladesh, Cambodia, India, Nepal). Data was collected through the migrants' medical records. Descriptive statistics were performed on socio-demographic variables. The diagnosed diseases were anonymously registered and classified according to the International Classification of Primary Care (ICPC-2). Conditional Inference Trees were used to perform a descriptive analysis of the sample and to detect the covariates with the strongest association with the variables Disease on arrival, Disease after arrival, ICPC on arrival and ICPC after arrival., Results: Analyzed observations were 9 857. 81.8% were men, median age was 23 (Interquartile range: 20.0-27.4). 70.3% of the sample came from Sub-Saharan Africa. 2 365 individuals (24%) arrived at the centre with at least one disease. On arrival, skin (27.71%), respiratory (14.46%), digestive (14.73%) and generic diseases (20.88%) were the most frequent. During the stay respiratory diseases were the most common (25.70%). The highest probability of arriving with a disease occurred in 2018 and during the period September-November 2016, in particular for people from the Horn of Africa. During this period and also in the first half of 2017, skin diseases were the most reported. In seasons with lower prevalence of diseases on arrival the most common disease code was generic for both men and women (usually fever or trauma)., Conclusions: This study provides information on the diverse diseases that affect the asylum seekers population. In our sample, the Horn of Africa was the most troubled area of arrival, with severe conditions frequently reported regarding skin diseases, in particular scabies. 2018 was the most critical year, especially for migrants from the Horn of Africa and Sub-Saharan Africa. During the stay at the camp, the prevalence of respiratory diseases increased. However, skin diseases remained the main issue for people from the Horn of Africa. Overall, the most reported diseases in the sample were dermatological, respiratory, digestive and generic diseases, both on arrival and during the stay. A better understanding of the health status of asylum seekers is an important factor to determine a more efficient reception and integration process and a better allocation of economic resources in the context of migrants' health care., (© 2022. The Author(s).)

Purpose: Cerebro-spinal fluid leak after transsphenoidal surgery for pituitary adenomas may be prevented by skull base reconstruction with fat autograft. However, graft changes may interfere with the interpretation of postoperative images. Our aim is to describe the radiological evolution of the fat autograft., Methods: A retrospective analysis was performed, including patients undergoing a transsphenoidal surgery for pituitary adenomas with a fat autograft for skull base reconstruction. Clinical and radiological data were collected, with assessment of fat autograft and extent of resection. Statistical analysis was performed using Kruskal-Wallis and Wilcoxon signed-rank test while Spearman's Rho was used to analyze the relationship between variables., Results: Seventy-two patients were included. Macroadenomas were diagnosed in 62 cases (86.1%) and in 21 cases an invasion of the cavernous sinus was described (29%). Gross total resection was achieved in 84.7% of cases. The volume of the fat graft significantly decreased between 3 months and 1 year after surgery (p = 0.01) and between 1 year and the last follow-up (mean 4.63 years, p < 0.01). Fat signal ratio significantly diminished between 3 months and 1 year in unenhanced and enhanced T1-weighted sequences (p = 0.04 and p = 0.02 respectively). Volume reduction was related to the decrease in signal ratio in unenhanced T1 sequences (p = 0.008)., Conclusion: Fat resorbs with time: almost 50% of the fat volume is lost during the first year after surgery and 60% is resorbed at 4.6 years. T1-signal, before and after gadolinium injection, also decreases during the first year, probably because of the progressive fibrosis of the graft. This information will contribute to the interpretation of postoperative images., (© 2022. The Author(s).)

Brain metastases (BM) are a common occurrence of systemic cancers. Technical improvements in neuroimaging offer additional tools for an early detection of BM, to target them precisely and differentiate these lesions from other cerebral pathologies. The therapeutic tools have also evolved from neurosurgery and whole brain therapy to include stereotactic radiosurgery, targeted and immune therapies. Given the numerous treatment options available, a multidisciplinary approach is essential to offer the patient a personalized approach to optimize the sequence and combination of treatments to offer the best outcome possible. This article aims to review key elements of diagnosis, risk stratification and modern treatment paradigms in the diagnosis and management of BM., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

(1) Background: Superior cerebellar peduncle (SCP) lesions are sparsely reported in the literature. The surgical approaches to the cerebello-mesencephalic region remain challenging. In this article, we present the extreme lateral supracerebellar infratentorial (ELSI) approach to treat a large hemorrhagic pilocytic astrocytoma of the SCP. (2) Methods: An 11-year-old boy, known for neurofibromatosis Type I, presented to the emergency department of our institution with symptoms and signs of intracranial hypertension. The cerebral magnetic resonance imaging (MRI) revealed a large hemorrhagic lesion centered on the SCP provoking obstructive hydrocephalus. Following an emergency endoscopic third ventriculocisternostomy (ETV), he underwent a tumor resection via an endoscope-assisted ELSI approach. (3) Results: ELSI approach allows for a wide exposure with direct access to lesions of the SCP. The post-operative course was uneventful, and the patient was discharged home on post-operative day 5. Post-operative MRI revealed a near total resection with a small residual tumor within the mesencephalon. (4) Conclusion: ELSI approach offers an excellent exposure with the surgical angles necessary for median and paramedian lesions. The park-bench position with appropriate head flexion and rotation offers a gravity-assisted relaxation of the tentorial and petrosal cerebellar surfaces. The endoscope can be an adjunct to illuminate the blind areas of the surgical corridor for an improved tumor resection without significant cerebellar retraction.

Introduction: The optimal surgical treatment for giant pituitary neuroendocrine tumors(GPitNETs) is debated., Research Question: The aim of this paper is to optimize the surgical management of these patients and to provide a consensus statement on behalf of the EANS Skull Base Section., Material and Methods: We constituted a task force belonging to the EANS skull base committee to define some principles for the management of GPitNETs. A systematic review was performed according to PRISMA guidelines to perform a meta-analysis on surgical series of GPitNETs. Weighted summary rates were obtained for the pooled extent of resection and according to the surgical technique. These data were discussed to obtain recommendations after evaluation of the selected articles and discussion among the experts., Results: 20articles were included in our meta-analysis, for a total of 1263 patients. The endoscopic endonasal technique was used in 40.3% of cases, the microscopic endonasal approach in 34% of cases, transcranial approaches in 18.7% and combined approaches in 7% of cases. No difference in terms of gross total resection (GTR) rate was observed among the different techniques. Pooled GTR rate was 36.6%, while a near total resection (NTR) was possible in 45.2% of cases. Cavernous sinus invasion was associated with a lower GTR rate (OR: 0.061). After surgery, 35% of patients had endocrinological improvement and 75.6% had visual improvement. Recurrent tumors were reported in 10% of cases., Discussion and Conclusion: After formal discussion in the working group, we recommend the treatment of G-PitNETs tumors with a more complex and multilobular structure in tertiary care centers. The endoscopic endonasal approach is the first option of treatment and extended approaches should be planned according to extension, morphology and consistency of the lesion. Transcranial approaches play a role in selected cases, with a multicompartmental morphology, subarachnoid invasion and extension lateral to the internal carotid artery and in the management of residual tumor apoplexy., (Crown Copyright © 2022 Published by Elsevier B.V. on behalf of EUROSPINE, the Spine Society of Europe, EANS, the European Association of Neurosurgical Societies.)

Background: The aim was to outline a methodology to monitor the impact of vaccinations in different countries comparing at two different times within countries and between countries the frequency of new cases and Covid-19 related deaths and the percentage of vaccinations conducted., Design and Methods: The 25 countries with the largest increase in SARS-CoV-2 cases on 8 August 2021 were evaluated. In each nation was calculated the proportion of Covid-19 deaths divided per new cases x 100 and the proportion of new cases per 1.000 inhabitants on 10 January 2021 (before vaccinations' distribution) and 8 August 2021 (when large percentage of the population had been vaccinated in many countries)., Results: The study shows that in the countries with the highest number of cases as of 8 August 2021, the proportion of vaccinations carried out in the population correlates negatively with both the proportion between Covid-19 dead people x100 infected people and with the rate of new cases. However, the proportion of vaccinations does not correlate with the differences in the two same indicators considered in the weeks observed, thus additional factors seem to play an important role., Conclusions: This work indicates that mass vaccination is associated with a lower spread of the pandemic and, to greater extent, with a lowering of mortality in infected people.

Among people with ST-segment elevation myocardial infarction (STEMI), high alexithymia was associated with delay to hospital arrival. High alexithymia could be a determinant of early death in the long term after STEMI. People with STEMI who participated in a survey in 2011, was tested about the state of life in 2021. The sample was divided into two cohorts (cut-off: TAS-20≥61 in 2011). The relationship between possible death occurred and having high alexithymia was calculated by comparing the mortality after 10 years in the two cohorts through the Cox' proportional hazard model. Status in life was verified on 39.3% of the sample. No differences were found regarding age, sex, high alexithymia between individuals on whom it was possible to verify the state in life and in whose it was not. In 2021, among people having high alexithymia in 2011, a higher risk of early death was found (RR=5.75, CI 95% 1.116-29.637).

Unilaterality of motor symptoms is a distinctive feature of Parkinson's Disease (PD) and represents an important co-factor involved in motor deficits and limitations of functional abilities including postural instability and asymmetrical gait. In recent times, an increasing number of studies focused on the characterization of such alterations, which have been associated with increased metabolic cost and risk of falls and may severely compromise their quality of life. Although a large number of studies investigated the gait alterations in people with PD (pwPD), few focused on kinematic parameters and even less investigated interlimb asymmetry under a kinematic point of view. This retrospective study aimed to characterize such aspects in a cohort of 61 pwPD (aged 68.9 ± 9.3 years) and 47 unaffected individuals age- and sex-matched (66.0 ± 8.3 years), by means of computerized 3D gait analysis performed using an optical motion-capture system. The angular trends at hip, knee and ankle joints of pwPD during the gait cycle were extracted and compared with those of unaffected individuals on a point-by-point basis. Interlimb asymmetry was assessed using angle-angle diagrams (cyclograms); in particular, we analyzed area, orientation, trend symmetry and range offset. The results showed that pwPD are characterized by a modified gait pattern particularly at the terminal stance/early swing phase of the gait cycle. Significant alterations of interlimb coordination were detected at the ankle joint (cyclogram orientation and trend symmetry) and at the hip joint (range offset). Such findings might be useful in clinical routine to characterize asymmetry during gait and thus support physicians in the early diagnosis and in the evaluation of the disease progression.

Background: Functioning of Social Behavioral Rhythms (SBRs) may affect resilience toward stressful events across different age groups. However, the impact of SBRs on the coronavirus disease of 2019 (COVID-19) in elder people is yet to ascertain, representing the aim of the present report., Design and Methods: Follow-up of a peer-reviewed randomized controlled trial on exercise on old adults (³65 years), concurrent to the onset of the pandemic-related lockdown. Post-RCT evaluations occurred after further 12 and 36 weeks since the beginning of the lockdown phase. People with Major Depressive Episode (MDE) at week-48 (follow-up endpoint) were deemed as cases, people without such condition were considered controls. MDE was ascertained using the Patient Health Questionnaire-9 (PHQ-9); SBRs functioning at week 12 onward, through the Brief Symptom Rating Scale (BSRS)., Results: Seventy-nine individuals (53.2%, females) entered the RCT-follow-up phase. The frequency of MDE did not significantly change before versus during lockdown (OR 2.60, CI95%=0.87-9.13). People with BSRS>1 standard deviation of the whole sample score at week-12 had an inflated risk of DE during lockdown (OR=5.6, 95%CI: 1.5-21.4) compared to those with lower BSRS scores. Such odd hold after excluding individuals with MDD at week-12. The post-hoc analysis could be potentially affected by selection bias., Conclusions: Overall, older adults were resilient during the first phase of the pandemic when functioning of pre-lockdown was still preserved, in contrast to the subsequent evaluations when the impairment of daily rhythms was associated with impaired reliance.

Background: This study aimed to verify, through a randomized controlled trial, whether a medium-intensity mixing/aerobic/anaerobic exercise (accessible to older adults even with mild chronic diseases) can effectively counteract depressive episodes. A characteristic of the trial was that the follow-up coincided (unscheduled) with the lockdown due to Covid-19., Methods: Participants (N=120) were randomized into an intervention group, performing physical exercise, and a control group. Participants, aged 65 years and older, belonged to both genders, living at home, and cleared a medical examination, were evaluated with a screening tool to detect depressive episodes, the PHQ9, at pre-treatment, end of the trial (12-week), and follow-up (48-week)., Results: A decrease in the frequency of depressive episodes after the trial (T1) was found in both groups; however, a statistically significant difference was observed only in the control group (p=0.0039). From T1 to follow-up (conducted during the lockdown), the frequency of depressive episodes increased in the control group, reaching a frequency equal to the time of study entry (p=0.788). In the experimental group, the frequency of depressive episodes did not change at the end of the trial but reached a statistically significant difference compared to the start of the study (p = 0.004) and was higher than the control group (p=0.028)., Conclusion: Moderate-intensity physical exercise can be conducted safely, benefitting older adults even suffering from mild chronic disorders. Physical exercise seems to guarantee a long-term preventive effect towards depressive symptoms, especially in serious stressful situations such as the lockdown due to the Covid-19 pandemic., Competing Interests: Dr. Mauro Giovanni Carta is the Editor-in-Chief and Dr. Luigi Minerba, Dr. Sergio Machado, and Dr. Antonio Preti are the Editorial Board Members of the journal Clinical Practice & Epidemiology in Mental Health., (© 2022 Carta et al.)

Background: Freezing of gait (FOG) is a disabling motor symptom occurring mainly in the advanced stage of Parkinson's disease (PD)., Methods: This review outlines the clinical manifestation of FOG and its relationship with levodopa treatment, the differential diagnosis with respect to other neurodegenerative and secondary forms and the available treatment., Results: We report the proposed models explaining the FOG phenomenon and summarize the available knowledge on FOG etiology's potential genetic contribution. A complete understanding of the mechanisms underlying FOG in PD is essential to find the best therapy. Different treatment options exist but are still not entirely successful, and often a combination of approaches is needed., Conclusions: Further studies focusing on the potential genetic role in FOG may increase the knowledge on the FOG etiology and pathophysiology, allowing further individualized treatment strategies for this very disabling phenomenon., (© 2021. Fondazione Società Italiana di Neurologia.)

Neurosurgery has traditionally been overtly focused on the study of anatomy and functions of cortical areas with microsurgical techniques aimed at preserving eloquent cortices. In the last two decades, there has been ever-increasing data emerging from advances in neuroimaging (principally diffusion tensor imaging) and clinical studies (principally from awake surgeries) that point to the important contribution of white matter tracts (WMT) that influence neurological function as part of a brain network. Major scientific consortiums worldwide, currently working on this human brain connectome, are providing evidence that is dramatically altering the manner in which we view neurosurgical procedures. The development of the telencephalic flexure, a major landmark during the human embryogenesis of the central nervous system (CNS), severely affects the cortical/subcortical anatomy in and around the sylvian fissure and thus the different interacting brain networks. Indeed, the telencephalic flexure modifies the anatomy of the human brain with the more posterior areas becoming ventral and lateral and associative fibers connecting the anterior areas with the previous posterior ones follow the flexure, thus becoming semicircular. In these areas, the projection, association, and commissural fibers intermingle with some WMT remaining curved and others longitudinal. Essentially the ultimate shape and location of these tracts are determined by the development of the telencephalic flexure. Five adult human brains were dissected (medial to lateral and lateral to medial) with a view to describing this intricate anatomy. To better understand the 3D orientation of the WMT of the region we have correlated the cadaveric data with the anatomy presented in the literature of the flexure during human neuro-embryogenesis in addition to cross-species comparisons of the flexure. The precise definition of the connectome of the telencephalic flexure is primordial during glioma surgery and for disconnective epilepsy surgery in this region., 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 ofinterest., (Copyright © 2022 González-López, Cossu, Thomas, Marston, Gómez, Pralong, Messerer and Daniel.)