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The present paper describes the investigation activities on the ground areas of a territory falling within the SIN Domitian Phlegrean and Agro Aversano Coast. It summarizes the general characteristics of the study area and the history of the human activities undertaken over time that may have caused a hazard to the environmental matrices. The results of sampling and analysis activities are shown with the evaluation of non-compliance with law requirements (acceptable limit values of concentration in the soil, subsoil and groundwaters).

Introduction: First-generation somatostatin receptor ligands (fg-SRLs) are the cornerstone of acromegaly treatment. Additional benefits were shown using high dose (HD) or high frequency (HF), relatively short-term regimens. Although several predictors of response to standard dose (SD)-fg-SRLs were reported, outcome biomarkers for HF administration are not yet available. Here, we aimed to identify predictors of response to long-term HF-fg-SRLs., Patients and Methods: A retrospective study was performed on 102 patients, treated with Lanreotide. Patients not controlled at 12 months of SD-Lanreotide (120 mg/28 days) were switched to HF-Lanreotide (120 mg/21 days) for additional 12 months., Results: Twenty-eight patients were controlled at 6 months of SD-Lanreotide (27.4%); 35 patients were controlled at 12 months of treatment (34.3%). Out of 67 patients treated with HF- Lanreotide, 18 (26.9%) were controlled at 6 months of treatment and remained controlled until 12 months. Both during SD and HF-Lanreotide administrations, IGF-I levels were reduced during the first six months of treatment (p < 0.001), without further significant reduction between 6 and 12 months of therapy. Response at 12 months of SD-Lanreotide was predicted by IGF-I reached at six months of SD-Lanreotide (p = 0.024). Response at 12 months of HF-Lanreotide treatment was predicted by IGF-I levels reached at six months of SD-Lanreotide treatment (p = 0.04) and six months of HF-Lanreotide treatment (p = 0.01)., Conclusion: Our results demonstrated that initial IGF-I levels during SD-Lanreotide predicted the biochemical outcome after 12 months of HF-Lanreotide. Patients in whom HF-Lanreotide did not normalize IGF-I after 6 months of treatment remained uncontrolled 12 months after starting this regimen., Competing Interests: Declarations. Institutional review board statement: All procedures performed in the study were in accordance with the ethical standards of the institutional review board and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the Institutional Review Board of the University Hospital “Fondazione Policlinico Universitario A. Gemelli IRCCS” in Rome, Italy (Protocol ID: 5132). Informed consent: Informed consent was obtained from all subjects involved in the study. Competing interests: All the authors declare no conflict of interest that could be perceived as prejudicing the impartiality of this paper. Sabrina Chiloiro recipient of Research grant to Institution from Ipsen, Pfizer, and Recordati. Andrea Giustina consultant for Amolyt, Ipsen, Pfizer, and Recordati and is Editor of Pituitary., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In patients with chronic kidney disease, particularly those in end-stage kidney failure and undergoing dialysis treatment, brain complications may arise, and their potential reversibility mainly hinges on timely diagnosis and intervention. Neurological symptoms may be non-specific ranging from slight or pronounced consciousness disturbance till coma, and imaging is the main tool to guide diagnosis and may reveal the underlying pathophysiological mechanism. Kidney impairment, causing a surge in blood pressure, increases the risk of Posterior Reversible Encephalopathy Syndrome and, leads to neurochemical alterations that result in uremic encephalopathy. In end-stage kidney failure patients, Posterior Reversible Encephalopathy Syndrome predominantly occurs in atypical locations, often involving the bilateral basal ganglia, and exhibit larger volumes compared to patients without kidney dysfunction. Uremic encephalopathy may involve the basal ganglia, white matter, and cortical or subcortical regions; in the latter case, imaging features resemble the typical location of Posterior Reversible Encephalopathy Syndrome. Dialysis Disequilibrium Syndrome, Osmotic Demyelination Syndrome, and Wernicke's encephalopathy are uncommon complications associated with dialysis. Each syndrome manifests distinct imaging patterns: Dialysis Disequilibrium Syndrome shows bilateral, patchy, diffuse white matter alterations; Osmotic Demyelination Syndrome causes central pontine and less often extrapontine lesions (involving bilateral basal ganglia, thalamus, and cerebral peduncles); Wernicke's encephalopathy determines symmetrical abnormalities in the thalamus, mammillary bodies, periaqueductal gray matter, midbrain tectal plate but the nature of brain edema associated with these complications remains controversial. Besides, in rare cases, overlapping imaging features may occur, and only the accurate patient's clinical history reconstruction along with laboratory examination results can lead to a better evaluation of MRI findings and underlying causes allowing prompt therapy., Competing Interests: Conflict of Interest There are no conflicts of interest, financial, or otherwise, (Copyright © 2024 Elsevier B.V. All rights reserved.)

A well-known link exists between cerebrovascular disease and chronic kidney disease. Cerebrovascular pathology in patients with kidney disease may be asymptomatic and occasionally discovered through neuroradiological examinations or it may present with neurological symptoms. Covert cerebrovascular lesions represent the earliest injuries associated with chronic kidney disease and primarily result from small vessel damage. These conditions often manifest incidentally, appearing as structural changes (such as lacunes, white matter lesions, enlarged perivascular spaces, cerebral microbleeds, and atrophy) as well as microstructural and hemodynamic alterations, detectable through routine and advanced functional MRIs. These alterations may be associated with a higher risk of stroke, cognitive decline, and dementia. Patients with end-stage renal disease or chronic kidney disease undergoing dialysis may be at increased risk of large-artery atherosclerosis, cardio-embolism, or small-vessel occlusion, and they may experience symptomatic acute ischemic strokes as rare complications. Currently, there are no established guidelines or standardized diagnostic protocols for preventing cerebrovascular disease in patients with kidney disease. Clinical and radiological studies are warranted to evaluate the usefulness of incorporating neuroimaging into the diagnostic work-up of these patients in order to improve prognosis and reduce diagnostic delays., Competing Interests: Conflicts of interest There are no conflicts of interest, financial, or otherwise., (Copyright © 2024. Published by Elsevier B.V.)

Background: Arterial dissection, a condition marked by the tearing of the carotid artery's inner layers, can result in varied clinical outcomes, including progression, stability, or spontaneous regression. Understanding these outcomes' underlying mechanisms is crucial for enhancing patient care, particularly with the increasing use of computer simulations in medical diagnostics and treatment planning. The aim of this study is to utilize computational analysis of blood flow and vascular wall to: (1) understand the pathophysiology of stroke-like episodes in patients with carotid artery dissection; and (2) assess the effectiveness of this method in predicting the evolution of carotid dissection., Methods: Utilizing contrast-enhanced magnetic resonance angiography (MRA), we segmented images of the patient's right internal carotid artery. These images were transformed into 3D solids for simulation in Ansys multifisic software, employing a two-way fluid structure interaction (FSI) analysis. Simulations were conducted across two wall conditions (atherosclerotic and normal) and three pressure states (hypotension, normotension, hypertension)., Results: The simulations indicated a significant pressure discrepancy between the true and false lumens of the artery. This suggests that flap motion and functional occlusion under hypertensive conditions could be the cause of the clinical episodes. Thrombotic risk and potential for dissection extension were not found to be critical concerns. However, a non-negligible risk of vessel dilation was assessed, aligning with the patient's clinical follow-up data., Conclusion: This study highlights specific hemodynamic parameters that could elucidate carotid artery dissection's mechanisms, offering a potential predictive tool for assessing dissection progression and informing personalized patient care strategies., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Bonura, Musotto, Iaccarino, Rossi, Calandrelli, Capone, Di Lazzaro and Pilato.)

Introduction: Stump syndrome is defined as a clinical syndrome resulting from a distal intracranial vessel embolic stroke due to an extracranial vessel occlusion. Similar to the anterior circulation, the recurrence of ischemic strokes in territories supplied by the posterior circulation in the presence of vertebral artery occlusion is termed Vertebral Artery Stump Syndrome (VASS)., Material and Methods: We conducted a literature review, identifying 72 patients with transient ischemic attacks (TIAs) or ischemic strokes attributed to VASS, according to Kawano criteria. We categorized all patients in two groups focusing on the therapeutic management those who underwent primary medical treatment and those who received endovascular or surgical treatment either in acute or chronic phase., Results: In the anticoagulant therapy group, only 1 patient had a stroke recurrence. Among the 4 on antiplatelets, all had recurrences, but 3 benefited from switching to anticoagulants or endovascular therapy. In the endovascular therapy group, worse outcomes were linked to acute large vessel occlusion. Endovascular treatment of the vertebral artery, in a chronic phase, was explored in literature for recurrent TIAs or minor strokes suggesting that this could be a viable therapeutic alternative when medical treatment failed in preventing recurrence of ischemic stroke., Conclusions: Some studies suggest that anticoagulant medical therapy may be beneficial for VASS and endovascular therapy has also been reported for selected patients. However, data on treatment outcomes and prognosis are still underreported, making treatment decisions challenging. Randomized Controlled Trials are needed to establish the optimal treatment approach., Competing Interests: Declaration of competing interest We declare that we have no conflicts of interest to disclose regarding the manuscript entitled "Vertebral Artery Stump Syndrome: A Comprehensive Review of Diagnosis and Management," submitted for consideration for publication in Journal of Stroke Cerebrovascular Disease. We have no financial interests, research funding, employment or leadership roles, intellectual property rights, consultancies, or personal relationships that could potentially influence or be perceived to influence the content of this manuscript. We affirm that the work is original, has not been previously published or submitted elsewhere, and that we have not received any financial support or compensation for the preparation, writing, or submission of this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Craniopharyngiomas continue to present a challenge in clinical practice due to their heterogeneity and unpredictable adherence to vital neurovascular structures, particularly the hypothalamus. This results in different degrees of hypothalamus-pituitary axis dysfunction and a lack of uniform consensus and treatment guidelines regarding optimal management. MRI and CT are complementary techniques in the preoperative diagnostic phase, enabling the precise definition of craniopharyngioma size, shape, and consistency, as well as guiding classification into histopathological subtypes and topographical categories. Meanwhile, MRI plays a crucial role in the immediate postoperative period and follow-up stages by identifying treatment-related changes and residual tumors. This pictorial essay aims to provide an overview of the role of imaging in identifying variables indicative of the adherence degree to the hypothalamus, hypothalamic-pituitary dysfunction, the extent of surgical excision, and prognosis. For a more comprehensive assessment, we choose to distinguish the following two scenarios: (1) the initial diagnosis phase, where we primarily discuss the role of radiological variables predictive of adhesions to the surrounding neurovascular structures and axis dysfunction which may influence the choice of surgical resection; (2) the early post-treatment follow-up phase, where we discuss the interpretation of treatment-related changes that impact outcomes.

The human blood-brain barrier (hBBB) is a highly specialized structure that regulates passage across blood and central nervous system (CNS) compartments. Despite its critical physiological role, there are no reliable in vitro models that can mimic hBBB development and function. Here, we constructed hBBB assembloids from brain and blood vessel organoids derived from human pluripotent stem cells. We validated the acquisition of blood-brain barrier (BBB)-specific molecular, cellular, transcriptomic, and functional characteristics and uncovered an extensive neuro-vascular crosstalk with a spatial pattern within hBBB assembloids. When we used patient-derived hBBB assembloids to model cerebral cavernous malformations (CCMs), we found that these assembloids recapitulated the cavernoma anatomy and BBB breakdown observed in patients. Upon comparison of phenotypes and transcriptome between patient-derived hBBB assembloids and primary human cavernoma tissues, we uncovered CCM-related molecular and cellular alterations. Taken together, we report hBBB assembloids that mimic the core properties of the hBBB and identify a potentially underlying cause of CCMs., Competing Interests: Declaration of interests Z.G. and L.D. have a pending patent application ("Vascularized brain organoids having a CCM-like feature and methods of making and use," U.S. Application no. 63/510,463) related to this research. S.Z. is a founder of Genemo, Inc., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study aims to evaluate in extremely premature infants the severity of brain structural injury causing total absence or near-total absence of cerebellar hemispheres by using MRI visual and volumetric scoring systems. It also aims to assess the role of the score systems in predicting motor outcome. We developed qualitative and quantitative MRI scoring systems to grade the overall brain damage severity in 16 infants with total absence or near-total absence of cerebellar hemispheres. The qualitative scoring system assessed the severity of macrostructural abnormalities of cerebellum, brainstem, supratentorial gray and white matters, ventricles while the quantitative scoring system weighted the loss of brain tissue volumes, and gross motor function classification system (GMFCS) was used to assess motor function at 1- and 5-year follow-ups.Positive correlations between both MRI scores and GMFCS scales were detected at follow-ups (p > 0.05), but only the volumetric score could identify those infants developing higher levels of motor impairment.Brain volumetric MRI offers an unbiassed assessment of prenatal brain damage. The quantitative scoring system, performed at term equivalent age, can be a helpful tool for predicting the long-term motor outcome in extremely preterm infants with a near-total absence of cerebellum., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Context: The prompt control of acromegaly is a primary treatment aim for reducing related disease morbidity and mortality. First-generation somatostatin receptor ligands (fg-SRLs) are the cornerstone of medical therapies. A non-negligible number of patients do not respond to this treatment. Several predictors of fg-SRL response were identified, but a comprehensive prognostic model is lacking., Objective: We aimed to design a prognostic model based on clinical and biochemical parameters, and pathological features, including data on immune tumor microenvironment., Methods: A retrospective, monocenter, cohort study was performed on 67 medically naïve patients with acromegaly. Fifteen clinical, pathological, and radiological features were collected and analyzed as independent risk factors of fg-SRLs response, using univariable and multivariable logistic regression analyses. A stepwise selection method was applied to identify the final regression model. A nomogram was then obtained., Results: Thirty-seven patients were fg-SRLs responders. An increased risk to poor response to fg-SRLs were observed in somatotropinomas with absent/cytoplasmatic SSTR2 expression (OR 5.493 95% CI 1.19-25.16, P = .028), with low CD68+/CD8+ ratio (OR 1.162, 95% CI 1.01-1.33, P = .032). Radical surgical resection was associated with a low risk of poor fg-SRLs response (OR 0.106, 95% CI 0.025-0.447 P = .002). The nomogram obtained from the stepwise regression model was based on the CD68+/CD8+ ratio, SSTR2 score, and the persistence of postsurgery residual tumor and was able to predict the response to fg-SRLs with good accuracy (area under the curve 0.85)., Conclusion: Although our predictive model should be validated in prospective studies, our data suggest that this nomogram may represent an easy to use tool for predicting the fg-SRL outcome early., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Dynamically organized chromatin complexes often involve multiplex chromatin interactions and sometimes chromatin-associated RNA 1-3 . Chromatin complex compositions change during cellular differentiation and ageing, and are expected to be highly heterogeneous among terminally differentiated single cells 4-7 . Here we introduce the multinucleic acid interaction mapping in single cells (MUSIC) technique for concurrent profiling of multiplex chromatin interactions, gene expression and RNA-chromatin associations within individual nuclei. When applied to 14 human frontal cortex samples from older donors, MUSIC delineated diverse cortical cell types and states. We observed that nuclei exhibiting fewer short-range chromatin interactions were correlated with both an 'older' transcriptomic signature and Alzheimer's disease pathology. Furthermore, the cell type exhibiting chromatin contacts between cis expression quantitative trait loci and a promoter tends to be that in which these cis expression quantitative trait loci specifically affect the expression of their target gene. In addition, female cortical cells exhibit highly heterogeneous interactions between XIST non-coding RNA and chromosome X, along with diverse spatial organizations of the X chromosomes. MUSIC presents a potent tool for exploration of chromatin architecture and transcription at cellular resolution in complex tissues., (© 2024. The Author(s).)

Background: Posterior synostotic plagiocephaly (PSP) impacts craniofacial skeleton. Study quantifies facial changes in children with PSP to investigate the impact of age and PSP severity at diagnosis on the facial dysmorphology., Material and Methods: High-resolution preoperative CT images of 22 infants with PSP were analyzed. They were divided according to the early or late age at time of diagnosis. Each group was further subdivided according to the severity of PSP evaluated by the cranial vault asymmetry index (CVAI): mild-moderate PSP (CVAI between 3 and 12%) and severe PSP (CVAI > 12%). Analysis of the facial complex was performed. Each group was compared with age-matched healthy subjects., Results: All children exhibited unilateral lambdoid suture synostosis. The "early" diagnosis group consisted of 7 children with mild-moderate PSP while the "late" diagnosis group of 15 children in which 6 children had mild-moderate and 9 children severe PSP. All children showed altered position of glenoid fossae and mandibular asymmetry characterized by reduced mandibular diagonal distance length on the affected side while the subgroup of children with severe PSP detected in "late" diagnosis group had also altered mandibular inclination and reduced midfacial depth on both sides., Conclusions: PSP causes cranial base dysmorphology which drives changes in facial complex growth; the severity of facial changes mainly depends on the severity of cranial vault dysmorphology detected by CVAI. Mandible reshapes early under the stress of altered biomechanical forces of the skull base while changes in the maxilla are secondary to the asymmetric growth of the mandible and occur only in severe cases., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: We aim to assess the role of a multidisciplinary approach in pituitary adenomas (PitNETs) classification, evaluate criteria concordance, and compare intraoperative assessments with post-operative MRIs for tumor remnants., Methods: Clinical, radiological, histological, and intra- and post-operative data of the treated PitNETs were extracted from prospectively created records. PitNETs were graded according to Trouillas, and the evaluation of the tumor remnants was recorded., Results: Of 362 PitNETs, 306 underwent surgery, with Trouillas grading assigned to 296. Eight-nine radiologically non-invasive PitNETs progressed to grades 1b (27), 2a (42), or 2b (20) due to proliferative or surgical invasiveness criteria. Twenty-six radiologically invasive tumors were graded 2b due to proliferative criteria. Surgical resection details and post-surgical MRI findings revealed that residual tumors were more common in grades 2a and 2b. During surgery, small tumor remnants were documented in 14 patients which were not visible on post-surgical MRI. Post-surgical MRIs identified remnants in 19 PitNETs not seen during surgery, located in lateral recesses of the sella (4), retrosellar (2), or suprasellar regions (7), along the medial wall of the cavernous sinus (6)., Conclusions: The Pituitary Board allows for the correct grading of PitNETs to be obtained and an accurate identification of high-risk patients who should undergo closer surveillance due to tumor remnants.

Chromatin-associated RNAs (caRNAs) form a relatively poorly recognized layer of the epigenome. The caRNAs reported to date are transcribed from the nuclear genome. Here, leveraging a recently developed assay for detection of caRNAs and their genomic association, we report that mitochondrial RNAs (mtRNAs) are attached to the nuclear genome and constitute a subset of caRNA, thus termed mt-caRNA. In four human cell types analyzed, mt-caRNAs preferentially attach to promoter regions. In human endothelial cells (ECs), the level of mt-caRNA-promoter attachment changes in response to environmental stress that mimics diabetes. Suppression of a non-coding mt-caRNA in ECs attenuates stress-induced nascent RNA transcription from the nuclear genome, including that of critical genes regulating cell adhesion, and abolishes stress-induced monocyte adhesion, a hallmark of dysfunctional ECs. Finally, we report increased nuclear localization of multiple mtRNAs in the ECs of human diabetic donors, suggesting many mtRNA translocate to the nucleus in a cell stress and disease-dependent manner. These data nominate mt-caRNAs as messenger molecules responsible for mitochondrial-nuclear communication and connect the immediate product of mitochondrial transcription with the transcriptional regulation of the nuclear genome., Competing Interests: KS, ZQ, DY, NM, XL, RC, YL, AT, SJ, MS, RD, BA, SP, PW, JL, RN, ZB No competing interests declared, JS JS is a co-founder of Translura, Inc, SZ SZ is a founder of Genemo, Inc, (© 2024, Sriram et al.)

Background: In adamantinomatous craniopharyngiomas, tumor topographical categories, cystic component volume, and magnetic resonance signal intensity may impact prognosis., Objective: To identify magnetic resonance imaging (MRI) variables associated with pituitary-hypothalamic axis dysfunction and predictive of outcome in children with cystic adamantinomatous craniopharyngiomas., Materials and Methods: We evaluated 40 preoperative MRIs of adamantinomatous craniopharyngiomas to classify tumor topography, volume, and signal intensity of the cystic components and peritumoral edema. Volumes and normalized signal intensity minimum values were extracted from coronal T2-weighted images (nT2 min ). Radiological variables were compared to pituitary-hypothalamic axis dysfunction-related clinical data and surgical outcomes., Results: Adamantinomatous craniopharyngiomas were categorized into five topographic classes (12 patients, sellar-suprasellar; seven patients, pseudo-intraventricular; six patients, strict intraventricular; 14 patients, secondary intraventricular; one patient, not strict intraventricular). All cases exhibited a predominant (30 patients, 80%) or total (10 patients, 20%) cystic tumor component and displayed low nT2 min percentage values compared to cerebrospinal fluid (42.3% [interquartile range 28.4-54.6%]). Significant associations between tumor topographic classes and pituitary dysfunction (P<0.001), and between peritumoral edema and hypothalamic dysfunction (P<0.001) were found. Considering extent of surgical removal and tumor relapse, volume of the cystic tumor component displayed a positive correlation (P=0.002; r=0.48; P=0.02; r=0.36), while nT2 min intensity values exhibited a negative correlation (P=0.01; r= - 0.40; P=0.028; r= - 0.34)., Conclusion: Severe hypothalamic-pituitary axis dysfunction is associated with tumors along the pituitary stalk and peritumoral edema. Tumor invasion of the third ventricle, tight adherence to the hypothalamus, larger volumes, and lower nT2 min intensity of the tumor cystic component are independent predictors of extent of adamantinomatous craniopharyngioma excision and recurrence., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To assess the role of FGFR2 mutations and sutural synostotic patterns on facial skeleton dysmorphology in children with syndromic craniosynostosis., Methods: Preoperative high-resolution CT images in 39 infants with syndromic craniosynostosis were evaluated. Patients were divided into infants with and without FGFR2 mutations; each group was split according to synostotic involvement of minor sutures/synchondroses: isolated or combined involvement of middle (MCF) and posterior cranial fossae (PCF). Quantitative analysis of the midface and mandible measures was performed. Each subgroup was compared with a group of age-matched healthy subjects., Results: Twenty-four patients with FGFR2 related syndromes were clustered in 3 subgroups: MCF + PCF (8 patients, 5.4 ± 1.75 months), MCF (8 patients, 3.62 ± 1.68 months), and PCF (8 patients, 2.75 ± 0.46 months). Fifteen no-FGFR2 patients were clustered in 2 subgroups: MCF + PCF (7 patients, 9.42 ± 0.78 months) and PCF (8 patients, 7.37 ± 2.92 months). Both FGFR2 and no-FGFR2 groups with involvement of minor sutures coursing in MCF showed more facial sutural synostoses. Children with minor suture/synchondrosis synostosis of MCF (MCF-PCF and MCF subgroups) showed altered position of glenoid fossa and mandibular inclination ([Formula: see text]), but children in the FGFR2 group had also reduced midfacial depth and maxillary length ([Formula: see text]). Children with minor suture/synchondrosis synostosis of PCF (PCF subgroups) had reduced posterior mandibular height, but those children in the FGFR2 group also showed reduced intergonion distance ([Formula: see text])., Conclusions: In children with syndromic craniosynostosis, both skull base and facial suture synostosis affect facial dysmorphology/hypoplasia. FGFR2 mutations may worsen facial hypoplasia both acting on bone development and causing an earlier premature closure of facial sutures., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To classify pituitary macroadenomas according to the Trouillas' grading system; to compare this grading system with T2 values of volumetric signal intensity to determine T2 values able to predict the final grade., Methods: A total of 106 patients with macroadenomas were grouped according to the grading system score combining proliferation and invasiveness criteria of Trouillas' classification. Normalized volumetric signal intensity values were extracted from coronal T2-weighted images (nT2mean, nT2Max, nT2min) and were compared with the final grading score system., Results: Thirty-three patients were in grade 1a (non-invasive, non-proliferative tumors), 17 patients in grade 1b (non-invasive, proliferative tumors), 36 patients in grade 2a (invasive, non-proliferative tumors), and 20 patients in grade 2b (invasive, proliferative tumors). No patient was in grade 3 (metastatic tumors). nT2Max and nT2min were the best quantitative values to discriminate invasive from non-invasive grades; in invasive grades, nT2Max intensity values were higher, and nT2min intensity values were lower than in non-invasive grades. Receiver operating characteristic analysis of nT2 values showed that nT2min values had a better diagnostic performance than nT2Max values because they allowed differentiating with a moderate accuracy invasive tumors (2a or 2b grades) from both non-invasive proliferative tumors (1b) and non-invasive-non proliferative tumors (1a) (2a vs 1b: AUC nT2min = 0.78, 2b vs 1b: AUC nT2min = 0.72, 2a vs 1a: AUC nT2min = 0.72, 2b vs 1a AUC nT2min = 0.69)., Conclusion: Volumetric nT2Max and nT2min values of MRI might be practical and non-invasive markers for assessing tumor invasiveness although nT2 min signal intensity values have more effects in discriminating tumor's invasive behavior., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The interphase genome is dynamically organized in the nucleus and decorated with chromatin-associated RNA (caRNA). It remains unclear whether the genome architecture modulates the spatial distribution of caRNA and vice versa. Here, we generate a resource of genome-wide RNA-DNA and DNA-DNA contact maps in human cells. These maps reveal the chromosomal domains demarcated by locally transcribed RNA, hereafter termed RNA-defined chromosomal domains. Further, the spreading of caRNA is constrained by the boundaries of topologically associating domains (TADs), demonstrating the role of the 3D genome structure in modulating the spatial distribution of RNA. Conversely, stopping transcription or acute depletion of RNA induces thousands of chromatin loops genome-wide. Activation or suppression of the transcription of specific genes suppresses or creates chromatin loops straddling these genes. Deletion of a specific caRNA-producing genomic sequence promotes chromatin loops that straddle the interchromosomal target sequences of this caRNA. These data suggest a feedback loop where the 3D genome modulates the spatial distribution of RNA, which in turn affects the dynamic 3D genome organization., (© 2023. Springer Nature Limited.)

Mitochondrial diseases (MDs) are heterogeneous genetic disorders characterized by mitochondrial DNA (mtDNA) defects, involving tissues highly dependent on oxidative metabolism: the inner ear, brain, eye, skeletal muscle, and heart. We describe adult patients with genetically defined MDs, characterizing hearing function and neuroimaging results. We enrolled 34 patients (mean age: 50.02 ± 15 years, range: 18-75 years; 20 females and 14 males) classified in four groups: MELAS, MIDD, PEO, and Encephalopathy/Polyneuropathy. Audiological evaluations included psychoacoustical tests (pure-tone and speech audiometry), electrophysiological tests (Auditory Brainstem Responses, ABRs), and Impedenzometry. Neuroimaging evaluations considered global MRI abnormalities or structural brain changes. In total, 19/34 patients carried the m.3243A > G mutation (6 affected by MELAS, 12 affected by MIDD, and 1 affected by PEO); 11 had an mtDNA deletion (all affected by PEO); 3 had nuclear genes associated with MDs (POLG1 and OPA1); and 1 patient had an mtDNA deletion without an identified nuclear gene defect (affected by PEO). Sensory neural, bilateral, and symmetrical hearing loss was present in 25 patients (73.5%) to different degrees: 9 mild, 9 moderate, 5 severe, and 2 profound. The severe/profound and mild hearing losses were associated with pantonal and high-frequency audiograms, respectively. Instead, moderate hearing losses were associated with both high-frequency (five cases) and pantonal (five cases) audiogram shapes. In addition, 21/25 patients showed a cochlear site of lesion (84%), and 4/25 (16%) showed a retrocochlear site. We found global MRI abnormalities or structural brain changes in 26/30 subjects (86.6%): 21 had white matter abnormalities, 15 had cortical atrophy, 10 had subcortical atrophy, 8 had basal nuclei involvement or cerebellar atrophy, 4 had stroke-like lesions or laminar necrosis, and 1 had cysts or vacuolated lesions. We concluded that genetic alterations are associated with different clinical presentations for both auditory function and neuroradiological findings. There is no fixed relationship between genotype and phenotype for the clinical conditions analyzed.

The four-dimensional nucleome (4DN) consortium studies the architecture of the genome and the nucleus in space and time. We summarize progress by the consortium and highlight the development of technologies for (1) mapping genome folding and identifying roles of nuclear components and bodies, proteins, and RNA, (2) characterizing nuclear organization with time or single-cell resolution, and (3) imaging of nuclear organization. With these tools, the consortium has provided over 2,000 public datasets. Integrative computational models based on these data are starting to reveal connections between genome structure and function. We then present a forward-looking perspective and outline current aims to (1) delineate dynamics of nuclear architecture at different timescales, from minutes to weeks as cells differentiate, in populations and in single cells, (2) characterize cis-determinants and trans-modulators of genome organization, (3) test functional consequences of changes in cis- and trans-regulators, and (4) develop predictive models of genome structure and function., Competing Interests: Declaration of interests J.D. is on the Scientific Advisory Board of Arima Genomics (San Diego, CA) and Omega Therapeutics (Cambridge, MA). F.A. is a shareholder of EarlyDiagnostics, Inc. S.A. is a member of the Chao-Ting Wu laboratory and holds or has patent filings pertaining to imaging and has held a sponsored research agreement with Bruker Inc. L.B. is a co-founder and scientific advisor of Stylus Medicine (Cambridge, MA). W.L. is a co-founder of Hub Biosciences. B.R. is a co-founder of and member of the Scientific Advisory Board of Arima Genomics (San Diego, CA) and a co-founder of Epigenome Technologies (San Diego, CA). J.S. is a Scientific Advisory Board member, consultant, and/or co-founder of Cajal Neuroscience, Guardant Health, Maze Therapeutics, Camp4 Therapeutics, Phase Genomics, Adaptive Biotechnologies, Scale Biosciences, Sixth Street Capital, Pacific Biosciences, and Prime Medicine. X.S. is a co-founder of Granule Therapeutics (San Francisco, CA). S.Z. is a founder and board member of Genemo, Inc (San Diego, CA)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

MRI plays a key role in the evaluation of post-treatment changes, both in the immediate post-operative period and during follow-up. There are many different treatment's lines and many different neuroradiological findings according to the treatment chosen and the clinical timepoint at which MRI is performed. Structural MRI is often insufficient to correctly interpret and define treatment-related changes. For that, advanced MRI modalities, including perfusion and permeability imaging, diffusion tensor imaging, and magnetic resonance spectroscopy, are increasingly utilized in clinical practice to characterize treatment effects more comprehensively. This article aims to provide an overview of the role of advanced MRI modalities in the evaluation of treated glioblastomas. For a didactic purpose, we choose to divide the treatment history in three main timepoints: post-surgery, during Stupp (first-line treatment) and at recurrence (second-line treatment). For each, a brief introduction, a temporal subdivision (when useful) or a specific drug-related paragraph were provided. Finally, the current trends and application of radiomics and artificial intelligence (AI) in the evaluation of treated GB have been outlined.

Agricultural and food waste recycling reduces natural resource losses, contributing significantly to the development of new green markets through the creation of redesigned products. In order to cycle valuable molecules, the peels from Italian cantaloupe ( Cucumis melo L.) cultivars were studied and successfully characterized for high-added biomolecules to verify their possible exploitation as wealthy biomasses. Peels were investigated for their cell wall-modifying and browning enzymes, as well as for total polyphenols, ortho -diphenols, flavonoids, tannins, and antioxidant properties. The results of the analyses displayed great promise in one of the three cultivars investigated. Later on, a preliminary study using the best peel extract as a dietary supplement was carried out by preparing fortified seawater to enhance its antioxidant power. The effects of storage time (60 days) were examined at two temperatures through the determination of the stability of the polyphenol content. The kinetic parameters of degradation were also calculated. The "enriched sea water" retained great antioxidant activity in refrigerated conditions, demonstrating that there is good potential for melon by-products to add their natural compounds for food fortification. These findings may provide valuable data for scale-up, from the lab to the pilot or industrial application., Competing Interests: The authors declare no conflict of interest.

Spatial transcriptomic tools and platforms help researchers to inspect tissues and cells with fine details of how they differentiate in expressions and how they orient themselves. With the higher resolution we get and higher throughput of expression targets, spatial analysis can truly become the core player for cell clustering, migration study, and, eventually, the novel model for pathological study. We present the demonstration of HiFi-slide, a whole transcriptomic sequencing technique that recycles used sequenced-by-synthesis flow cell surfaces to a high-resolution spatial mapping tool that can be directly applied to tissue cell gradient analysis, gene expression analysis, cell proximity analysis, and other cellular-level spatial studies.

Purpose: To develop a neuroradiological score in patients with deep cerebral venous thrombosis (DCVT), capable of assessing extension of intracranial changes and venous occlusion at diagnosis; to assess the relationship between neuroradiological and clinical features at follow-up., Material and Methods: In 14 patients with DCVT, we developed 2 score systems on non-enhanced and contrast-enhanced CT: Intracranial Imaging Score (IIS) and Venous Occlusion Imaging Score (VOIS). ISS considers parenchymal venous strokes, hemorrhage, mass effect, and hydrocephalus; VOIS evaluates unilateral or bilateral venous occlusion extension. Modified Rankin Scale (mRS) and vessel recanalization status were assessed at follow-up., Results: At diagnosis, higher IIS was related to bilateral venous thrombosis involvement (p 0,02; r:0,60), but parenchymal strokes were not related to venous occlusion extension (unilateral or bilateral) (p > 0,05). Moreover, the symptoms' onset time did not correlate with the severity scores (p > 0,05). At follow-up, 8 out of 14 patients showed good clinical outcomes with complete recanalization and neurological improvement, 1 patient showed a poor neurological outcome, whereas 5 patients died within 1 week. Positive correlations were found between IIS and mRS (p 0,003, r = 0,73), between IIS and vessels' recanalization status (p 0,002, r = 0,75), and between vessels' recanalization status and mRS (p < 0,001, r = 0,98)., Conclusion: Neuroradiological scores may enhance diagnostic accuracy, and they may have a predictive significance. In patients with DCVT, although intracranial involvement was not influenced by symptoms' onset time or extension of venous occlusion, clinical outcome was related to both intracranial involvement and venous recanalization state. Collateral venous drainage status may counterbalance the thrombotic process improving prognosis., (© 2023. Fondazione Società Italiana di Neurologia.)

During the SARS-CoV2 pandemic, several cases of Posterior Reversible Encephalopathy Syndrome (PRES) and of Reversible Cerebral Vasoconstriction Syndrome (RCVS) in COVID-19 patients have been reported, but the link between these syndromes and COVID-19 is unclear. We performed a systematic review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to evaluate whether SARS-CoV2 infection or the drugs used to treat it could be deemed potential risk factors for PRES or RCVS. We performed a literature search. We found 70 articles (60 on PRES and 10 on RCVS) concerning n = 105 patients (n = 85 with PRES, n = 20 with RCVS). We analyzed the clinical characteristics of the two populations separately, then performed an inferential analysis to search for other independent risk factors. We found fewer than usual PRES-related (43.9%) and RCVS-related (45%) risk factors in patients with COVID-19. Such a low incidence of risk factors for PRES and RCVS might suggest the involvement of COVID-19 as an additional risk factor for both diseases due to its capability to cause endothelial dysfunction. We discuss the putative mechanisms of endothelial damage by SARS-CoV2 and antiviral drugs which may underlie the development of PRES and RCVS., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

(1) Background: Hypertension is a complex, multifactorial disease that is caused by genetic and environmental factors. Apart from genetic predisposition, the mechanisms involved in this disease have yet to be fully understood. We previously reported that LEENE (lncRNA enhancing endothelial nitric oxide expression, transcribed from LINC00520 in the human genome) regulates endothelial cell (EC) function by promoting the expression of endothelial nitric oxide synthase (eNOS) and vascular growth factor receptor 2 (VEGFR2). Mice with genetic deletion of the LEENE/LINC00520 homologous region exhibited impaired angiogenesis and tissue regeneration in a diabetic hindlimb ischemia model. However, the role of LEENE in blood pressure regulation is unknown. (2) Methods: We subjected mice with genetic ablation of leene and wild-type littermates to Angiotensin II (AngII) and monitored their blood pressure and examined their hearts and kidneys. We used RNA-sequencing to identify potential leene -regulated molecular pathways in ECs that contributed to the observed phenotype. We further performed in vitro experiments with murine and human ECs and ex vivo experiments with murine aortic rings to validate the select mechanism. (3) Results: We identified an exacerbated hypertensive phenotype of leene -KO mice in the AngII model, evidenced by higher systolic and diastolic blood pressure. At the organ level, we observed aggravated hypertrophy and fibrosis in the heart and kidney. Moreover, the overexpression of human LEENE RNA, in part, restored the signaling pathways impaired by leene deletion in murine ECs. Additionally, Axitinib, a tyrosine kinase inhibitor that selectively inhibits VEGFR suppresses LEENE in human ECs. (4) Conclusions: Our study suggests LEENE as a potential regulator in blood pressure control, possibly through its function in ECs., Competing Interests: J.W.R. received industry-sponsored research grant from Pfizer on an unrelated work. S.Z. is a founder and board member of Genemo Inc, San Diego, CA, USA.

Growth Hormone-secreting adenomas exhibits variable biological behavior and heterogeneous natural history, ranging from small adenomas and mild disease, to invasive and aggressive neoplasms with more severe clinical picture. Patients not cured or controlled after neurosurgical and first-generation somatostatin receptor ligands (SRL) therapy could require multiple surgical, medical and/or radiation treatments to achieve disease control. To date, no clinical, laboratory, histopathological, or neuroradiological markers are able to define the aggressiveness or predict the disease prognosis in patients with acromegaly. Therefore, the management of these patients requires careful evaluation of laboratory assessments, diagnostic criteria, neuroradiology examinations, and neurosurgical approaches to choose an effective and patient-tailored medical therapy. A multidisciplinary approach is particularly useful in difficult/aggressive acromegaly to schedule multimodal treatment, which includes radiation therapy, chemotherapy with temozolomide and other, recent emerging treatments. Herein, we describe the role of the different members of the multidisciplinary team according to our personal experience; a flow-chart for the therapeutic approach of difficult/aggressive acromegaly patients is proposed., 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 Bianchi, Chiloiro, Giampietro, Gaudino, Calandrelli, Mazzarella, Caldarella, Rigante, Gessi, Lauretti, De Marinis, Olivi, Pontecorvi and Doglietto.)

To develop a radiological score system to assess the severity of acute cerebellitis (AC) and to compare radiological severity score at the onset to cerebellar atrophy at follow-up. Clinical and MRI findings were recorded in 16 patients with AC. Radiological severity score considering topographic patterns, gray/white matter involvement, enhancement, tonsillar herniation or hydrocephalus development and clinical severity score taking into account clinical symptoms were assessed for each patient at the onset of the symptoms. Radiological and neurological sequelae were assessed at follow-up. At symptoms onset, clinical severity scale ranged from mild to severe and radiological severity score ranged from 3 to 7 with higher scores indicating a greater severity. The cut-off value of 5 for radiological score well segregated severe patients defined by clinical scale. A significant correlation between clinical scale and radiological severity scores (p < 0.001, r = 0.75) was found. At follow-up visit, all children developed cerebellar atrophy and 5 children showed neurologic sequelae while adults showed complete resolution without atrophy. Patients in whom atrophy was not observed had both older ages (p < 0.001) and a focal cerebellar involvement (p = 0.03). In patients with AC, radiological severity score may be a useful tool in evaluating clinical severity, but it is not capable to predict neither neurological sequelae nor evolution towards atrophy. Cerebellar atrophy, observed in children with AC, may be caused by several factors such as the age of patient and the extension of cerebellar involvement and it may be counterbalanced by neuronal restoring processes due to neuroplasticity., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: We performed a retrospective qualitative and quantitative evaluation of the sutural changes during the physiological growth to define the age-related ossification stages of major and minor skull sutures or synchondroses., Methods: A total of 390 healthy subjects, examined for cranio-facial trauma and whose CT scans turned out to be normal, were clustered into homogenous age-matched groups ranged from birth to 90 years. High-resolution CT was used to assess the degree of sutural closure according to a 3-grade scoring system, the sutural pattern, the width, and the density of the gap calculated as the average of two or three ROIs along each suture/synchondrosis., Results: The identification of a definite pattern depended on the suture's type, the closure degree, and the width of the gap (p < 0.001). The interdigitation process was more intricate for most of vault sutures than the skull base sutures/synchondroses. Closing grades 1, 2, and 3 were associated to an identifiable sutural pattern and the cutoff value of 1.45 mm of the gap width allowed to detect an identifiable sutural pattern with the best combination of sensitivity (97%) and specificity (98%). Age and sutural closing degree were inversely related to gap width while positively related to the gap density (p < 0.001)., Conclusion: The sutural ossification is an age-related process, distinctive for each suture, and synchondrosis; it occurs neither according to a predefined order along sutural arches nor following a sequential distribution in the cranial fossae, and some sutures continued their growth process during lifetime., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Impaired angiogenesis in diabetes is a key process contributing to ischemic diseases such as peripheral arterial disease. Epigenetic mechanisms, including those mediated by long noncoding RNAs (lncRNAs), are crucial links connecting diabetes and the related chronic tissue ischemia. Here we identify the lncRNA that enhances endothelial nitric oxide synthase (eNOS) expression (LEENE) as a regulator of angiogenesis and ischemic response. LEENE expression was decreased in diabetic conditions in cultured endothelial cells (ECs), mouse hind limb muscles, and human arteries. Inhibition of LEENE in human microvascular ECs reduced their angiogenic capacity with a dysregulated angiogenic gene program. Diabetic mice deficient in Leene demonstrated impaired angiogenesis and perfusion following hind limb ischemia. Importantly, overexpression of human LEENE rescued the impaired ischemic response in Leene-knockout mice at tissue functional and single-cell transcriptomic levels. Mechanistically, LEENE RNA promoted transcription of proangiogenic genes in ECs, such as KDR (encoding VEGFR2) and NOS3 (encoding eNOS), potentially by interacting with LEO1, a key component of the RNA polymerase II-associated factor complex and MYC, a crucial transcription factor for angiogenesis. Taken together, our findings demonstrate an essential role for LEENE in the regulation of angiogenesis and tissue perfusion. Functional enhancement of LEENE to restore angiogenesis for tissue repair and regeneration may represent a potential strategy to tackle ischemic vascular diseases.

Purpose: To assess the main imaging and clinical features in adult- and pediatric-onset atypical teratoid rhabdoid tumor (ATRT) in order to build a predefined pathway useful for the diagnosis., Methods: We enrolled 11 ATRT patients (10 children, one adult) and we conducted a literature search on PubMed Central using the key terms "adult" or "pediatric" and "atypical teratoid/rhabdoid tumor". We collected clinical and neuroradiological data reported in previous studies and combined them with those from our case series. A three step process was built to reach diagnosis by identifying the main distinctive clinical and imaging features., Results: Clinical evaluation: neurological symptoms were nonspecific. ATRT was more frequent in children under 3 years of age (7 out of 10 children) and infratentorial localization was reported more frequently in children under the age of 24 months. Midline/off-midline localization was influenced by the age., Imaging Findings: Preferential location near the ventricles and liquor spaces and the presence of eccentric cysts were hallmark for ATRT; higher frequency of peripheral cysts was detected in children and in the supratentorial compartment (five out of eight patients with solid-cystic ATRT). Leptomeningeal dissemination at diagnosis was common (5 out of 10 children), while intratumoral hemorrhage, calcifications, and high cellularity were non-specific findings. Histopathological analysis: specific immunohistochemical markers were essential to confirm the diagnosis., Conclusion: In younger children, a bulky, heterogeneous mass with eccentric cystic components and development near ventricles or cisternal spaces may be suggestive of ATRT. ATRT diagnosis is more challenging in adults and relies exclusively on neuropathological examination.

Purpose: Thrombus permeability has been related to clot composition and treatment outcomes in stroke patients undergoing reperfusion therapies. The aim of this study was to evaluate whether thrombus perviousness, evaluated by multiphase computed tomography angiography (mCTA), is associated with distal embolization risk., Methods: We interrogated our dataset of acute ischemic stroke (AIS) patients involving the M1 segment of the middle cerebral artery (MCA) who had undergone mechanical thrombectomy, and we calculated thrombus average attenuation measurement (dHU) on non-contrast CT (NCCT) and clot perviousness on mCTA. dHU was calculated as the difference between the thrombus HU average value (tHU) and the HU average value on the contralateral side (cHU), while perviousness was calculated as the difference in mean clot density on mCTA and NCCT both in arterial (Perviousness pre-post-1) and delayed (Perviousness pre-post 2) phases., Results: A total of 100 patients (53 females (53%), mean age 72.74 [± 2.31]) with M1 occlusion were available for analysis. Perviousness, calculated between baseline and arterial phase of mCTA (Perviousness pre-post1), was lower in patients with distal embolization ( p = 0.05), revealing an association between reduced perviousness and distal embolization risk. Logistic regression showed that thrombus perviousness calculated on the arterial phase of mCTA (OR, 0.66; 95% CI, 0.44-0.99] ( p = 0.04)) and the contact aspiration technique (OR, 0.39; 95% CI, 0.15-1.02] ( p = 0.05)) were protecting factors against distal embolization., Conclusion: Our study showed an association between reduced perviousness and distal embolization, suggesting that perviousness evaluation may be a useful neuroimaging biomarker in predicting distal embolization risk during mechanical thrombectomy.

Achondroplasia is an autosomal dominant genetic disease representing the most common form of human skeletal dysplasia: almost all individuals with achondroplasia have identifiable mutations in the fibroblast growth factor receptor type 3 ( FGFR3 ) gene. The cardinal features of this condition and its inheritance have been well-established, but the occurrence of feeding and nutritional complications has received little prominence. In infancy, the presence of floppiness and neurological injury due to foramen magnum stenosis may impair the feeding function of a newborn with achondroplasia. Along with growth, the optimal development of feeding skills may be affected by variable interactions between midface hypoplasia, sleep apnea disturbance, and structural anomalies. Anterior open bite, prognathic mandible, retrognathic maxilla, and relative macroglossia may adversely impact masticatory and respiratory functions. Independence during mealtimes in achondroplasia is usually achieved later than peers. Early supervision of nutritional intake should proceed into adolescence and adulthood because of the increased risk of obesity and respiratory problems and their resulting sequelae. Due to the multisystem involvement, oral motor dysfunction, nutrition, and gastrointestinal issues require special attention and personalized management to facilitate optimal outcomes, especially because of the novel therapeutic options in achondroplasia, which could alter the progression of this rare disease.

Background: Most infants and children with achondroplasia show delayed motor skill development; however, some patients may have clinical consequences related to cranio-cervical junction stenosis and compression., Purpose: To assess, using brain magnetic resonance imaging (MRI), quantitative variables linked to neuromotor impairment in achondroplasic children., Material and Methods: In total, 24 achondroplasic children underwent pediatric neurological assessment and were grouped in two cohorts according to relevant motor skill impairment. Achondroplasic children with (n=12) and without (n=12) motor symptoms were identified, and brain MRI scans were quantitatively evaluated. 3D fast spoiled gradient echo T1-weighted images were used to assess: supratentorial intracranial volumes (SICV); supratentorial intracranial brain volume (SICBV); SICV/SICBV ratio; posterior cranial fossa volume (PCFV); posterior cranial fossa brain volume (PCBFV); PCFV/PCFBV ratio; ventricular and extra-ventricular cerebrospinal fluid (CSF) volumes; foramen magnum (FM) area; and jugular foramina (JF) areas., Results: In both groups, SICV/SICBV ratio, supratentorial ventricular and extra-ventricular space volumes were increased while SICBV was increased only in the asymptomatic group ( P  < 0.05). PCFV/PCFBV ratio, IV ventricle, infratentorial extra-ventricular spaces volumes were reduced ( P  < 0.05) in the symptomatic group while PCFBV was increased only in the asymptomatic group ( P  < 0.05). Foramen magnum (FM) area was more reduced in the symptomatic group than the asymptomatic group ( P  < 0.05) but no correlation between FM area and ventriculomegaly was found ( P  > 0.05)., Conclusion: Evaluation of the FM area together with infratentorial ventricular and extra-ventricular space volume reduction may be helpful in differentiating patients at risk of developing motor skill impairment. Further investigation is needed to better understand the temporal profile between imaging and motor function in order to propose possible personalized surgical treatment.

Purpose: Once believed a result of pathophysiological correlations, the association between Chiari 1 malformation (CM1) and epilepsy has since been considered as a coincidence, due to missing etiologic or clinical matching points. At present, the problem is being newly debated because of the increasing number of CM1 diagnoses, often among children with seizures. No specific studies on this topic are available yet. The present study aimed at updating the information on this topic by reporting on a series of children specifically enrolled and retrospectively analyzed for this purpose. Methods: All children admitted between January 2015 and June 2020 for epilepsy and CM1 were considered (Group 1). They were compared with children admitted in the same period for symptoms/signs related to CM1 and/or syringomyelia (Group 2). Syndromic patients were excluded, as well as those with tumoral or other overt intracranial lesions. All patients received a complete preoperative work-up, including MRI and EEG. Symptomatic children with CM1/syringomyelia were operated on. The pertinent literature was reviewed. Results: Group 1 was composed of 29 children (mean age: 6.2 years) showing CM1 and epilepsy with several types of seizures. A share of 27% had CM1-related symptoms and syringomyelia. The mean tonsillar ectopia was 7.5 mm. Surgery was performed in 31% of cases. Overall, 62% of children are currently seizure-free (including 5/9 children who were operated on). Tonsillar herniation and syringomyelia regressed in 4/9 cases and 4/8 cases, improved in 4/9 cases and 3/8 cases, and remained stable in 1/9 and 1/8 cases, respectively. CM1 signs/symptoms regressed completely in 6/8 cases and improved or remained stable in one case in each of the two remaining patients. Group 2 consisted of 77 children (mean age: 8.9 years) showing symptoms of CM1 (75%) and/or syringomyelia (39%). The mean tonsillar ectopia was 11.8 mm. Non-specific EEG anomalies were detected in 13 children (17%). Surgery was performed in 76.5% of cases (18 children were not operated on because of oligosymptomatic). Preoperative symptoms regressed in 26%, improved in 50%, remained stable 22%, and worsened in 2%; CM1 radiologically regressed in 39%, improved in 37%, remained unchanged in 22%, and worsened in 2%; and syringomyelia/hydromyelia regressed in 61%, improved in 30%, and was stable in 9%. No statistically significant differences between the two groups were detected regarding the M/F ratio, presence of syringomyelia/hydromyelia, or CM1/syringomyelia outcome; moreover, no correlation occurred between seizure-free condition and PF decompression in Group 1, or between disappearance of EEG anomalies and PF decompression in Group 2. A significant difference between the two groups was noticed regarding the mean age at admission (p = 0.003), amount of tonsillar herniation (p < 0.00001), and PF decompression (p = 0.0001). Conclusions: These findings do not support clinical correlations between CM1 and epilepsy. Their course depends on surgery and antiepileptic drugs, respectively. The analysis of the literature does not provide evidence of a relationship between seizures and cerebellar anomalies such as CM1. Rather than being linked to a syndrome that could explain such an association, the connection between the two now has to be considered to be random.

Background: Malignant middle cerebral artery infarction (mMCA) is a devastating disease with rates of fatality as high as 80%. Decompressive hemicraniectomy (DHC) reduces mortality, but many survivors inevitably remain severely disabled. This study aimed to analyze patients with mMCA undergoing DHC or best medical treatment (BMT) baseline characteristics and factors linked to therapeutic choice and determinants of prognosis., Methods: We recorded clinical and radiological features of patients undergoing BMT or DHC. The two groups were compared for epidemiology, clinical presentation, neuroimaging, and prognosis. Regression analysis was performed to identify predictors of surgical treatment and outcome., Results: One hundred twenty-five patients were included (age 67.41 ± 1.39 yo; 65 M). Patients undergoing DHC (N = 57) were younger (DHC 55.71 ± 1.48 yo vs. BMT 77.22 ± 1.38) and had midline shift (DHC 96.5% (55/57) vs. BMT 35.3% (24/68), a larger volume of the affected hemisphere and reduced ventricles volume as compared to BMT. The chance of surgery depended on age (Exp(B) = 0.871, p < 0.001), clinical status at onset (NIHSS Exp(B) = 0.824, p = 0.030) and volume of the ventricle of the affected hemisphere (Exp(B) = 0.736, p = 0.006). Death rate during admission was significantly lower for DHC (DHC 15% (6/41) vs BMT 71.7% (38/53), Fisher's test = 30.234, p < 0.001)., Conclusion: Although DHC may cause prolonged hospitalization and long-term disabled patients, it is a lifesaving therapy that should be considered for selected patients with mMCA but perioperative complications and cost-utility should be considered. Patients and families should be correctly counseled about this therapeutic choice and its short- and long-term consequences., Competing Interests: Declaration of Competing Interest The Authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We evaluated the accuracy of the quantitative and semiquantitative analysis in detecting regional atrophy patterns and differentiating mild cognitive impairment patients who remain stable (aMCI-S) from patients who develop Alzheimer's disease (aMCI-AD) at clinical follow-up. Baseline magnetic resonance imaging was used for quantitative and semiquantitative analysis using visual rating scales. Visual rating scores were related to gray matter thicknesses or volume measures of some structures belonging to the same brain regions. Receiver operating characteristic (ROC) analysis was performed to assess measures' accuracy in differentiating aMCI-S from aMCI-AD. Comparing aMCI-S and aMCI-AD patients, significant differences were found for specific rating scales, for cortical thickness belonging to the middle temporal lobe (MTL), anterior temporal (AT), and fronto-insular (FI) regions, for gray matter volumes belonging to MTL and AT regions. ROC curve analysis showed that middle temporal atrophy, AT, and FI visual scales showed better diagnostic accuracy than quantitative measures also when thickness measures were combined with hippocampal volumes. Semiquantitative evaluation, performed by trained observers, is a fast and reliable tool in differentiating, at the early stage of disease, aMCI patients that remain stable from those patients that may progress to AD since visual rating scales may be informative both about early hippocampal volume loss and cortical thickness reduction., Competing Interests: Conflict of interest: Cesare Colosimo declares that he is scientific consultant for Bracco Diagnostics Inc. and Bayer HealthCare. The other authors do not state the conflict of interest., (© 2022 Rosalinda Calandrelli et al., published by De Gruyter.)

The spread of smartphones and mobile-Health (m-health) has progressively changed clinical practice, implementing access to medical knowledge and communication between doctors and patients. Dedicated software called Applications (or Apps), assists the practitioners in the various phases of clinical practice, from diagnosis to follow-up and therapy management. The impact of this technology is even more important in diseases such as stroke, which are characterized by a complex management that includes several moments: primary prevention, acute phase management, rehabilitation, and secondary prevention. This review aims to evaluate and summarize the available literature on Apps for the clinical management of stroke. We described their potential and weaknesses, discussing potential room for improvement. Medline databases were interrogated for studies concerning guideline-based decision support Apps for stroke management and other medical scenarios from 2007 (introduction of the first iPhone) until January 2022. We found 551 studies. Forty-three papers were included because they fitted the scope of the review. Based on their purpose, Apps were classified into three groups: primary prevention Apps, acute stroke management Apps, and post-acute stroke Apps. We described the aim of each App and, when available, the results of clinical studies. For acute stroke, several Apps have been designed with the primary purpose of helping communication and sharing of patients' clinical data among healthcare providers. However, interactive systems Apps aiming to assist clinicians are still lacking, and this field should be developed because it may improve stroke patients' management.

Background and Purpose: Whole-spine magnetic resonance imaging (MRI) studies, to identify structural abnormalities associated with the development of symptomatic spinal stenosis in achondroplasia., Methods: Forty-two subjects with achondroplasia were grouped into four age-related categories. Congenital spinal deformities (vertebral body and disc height, interpedicular distance), acquired spinal degenerative changes, thoracic kyphotic (TK) angle, thoracolumbar kyphotic (TLK) angle, spinal canal widths were evaluated by MRI., Results: Patients in the first three groups were asymptomatic and younger (group 1: 4.4 ± 0.78 years; group 2: 8.18 ± 0.60 years; group 3: 10.95 ± 0.93 years) than the symptomatic group (group 4: 23 ± 1.30 years). Patients showed height of vertebral bodies, whole canal width, and average lumbar interpedicular distance reduced. Discs degeneration was more pronounced in the lumbar region and in symptomatic adult patients. TK and TLK angles showed a positive correlation with age (p &lt; .05, r = .42; p &lt; .05, r = .41), whereas thoracic and thoracolumbar canal width had a negative correlation (p &lt; .05, r = -.69; p &lt; .05, r = -.58). A negative correlation between lumbar discs degeneration and canal width was found only at L1-L3 level (p &lt; .05, r = -.35). At L1-L3, the canal width cutoff value of .59 allowed the differentiation between asymptomatic and symptomatic patients (area under the curve of .966, p &lt; .0001)., Conclusion: In achondroplasia, the spinal canal narrowing, due to accelerated degenerative changes, is a predisposing factor of symptomatic lumbar spinal stenosis. Lumbar canal MRI is a helpful tool to detect the risk of the development of neurological symptoms; in adult patients, a stenosis higher than 60% of upper lumbar canal could be a critical value for the onset of neurological symptoms., (© 2022 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Background: The aim of this study is to develop a prediction model for trismus (maximal interincisal distance equal to or less than 35 mm) based on a multivariable analysis of dosimetric and clinical factors., Methods: The maximum inter-incisal opening (MIO) of hean and neck cancer (HNC) patients who underwent radiotherapy (RT) ± concurrent chemotherapy with radical intent, was prospectively measured prior to RT (baseline) and 6 months post-RT. The outcome variable is trismus. The potential risk factors (clinical and dosimetric) were first screened by univariate analysis and then by multivariate analysis. At the end of this process, we used the features identified as relevant, to fit a logistic regression model and calculate the probability of observed trismus during the 6-month follow-up after RT., Results: One hundred and four consecutive patients were included (mean age 63 years, range 25-87), 68 males, 36 females. In the univariate analysis, the MIO at baseline, as an independent variable, and several V doses of different masticatory structures were found as significant. Additionally, using a bivariate model, a feature selection process was performed. Finally, we considered as best performing model the MIO at baseline and V 42 at masseter muscles. The area under curve (AUC) of Receiver Operating Characteristic (ROC) curve value was 0.8255 (95% CI 0.74-0.9). The Hosmer and Lemeshow goodness-of-fit test, used to calibrate our model, was not-significant., Conclusions: A prediction nomogram was developed to assess trismus risk in planning process. An external validation of the model is required to apply it for current clinical use., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: To investigate the potentialities of radiomic analysis and develop radiomic models to predict the skull dysmorphology severity and post-surgical outcome in children with isolated sagittal synostosis (ISS)., Materials and Methods: Preoperative high-resolution CT scans of infants with ISS treated with surgical correction were retrospectively reviewed. The sagittal suture (ROI&#95;entire) and its sections (ROI&#95;anterior/central/posterior) were segmented. Radiomic features extracted from ROI&#95;entire were correlated to the scaphocephalic severity, while radiomic features extracted from ROI&#95;anterior/central/posterior were correlated to the post-surgical outcome. Logistic regression models were built from selected radiomic features and validated to predict the scaphocephalic severity and post-surgical outcome., Results: A total of 105 patients were enrolled in this study. The kurtosis was obtained from the feature selection process for both scaphocephalic severity and post-surgical outcome prediction. The model predicting the scaphocephalic severity had an area under the curve (AUC) of the receiver operating characteristic of 0.71 and a positive predictive value of 0.83 for the testing set. The model built for the post-surgical outcome showed an AUC (95% CI) of 0.75 (0.61;0.88) and a negative predictive value (95% CI) of 0.95 (0.84;0.99)., Conclusion: Our results suggest that radiomics could be useful in quantifying tissue microarchitecture along the mid-suture space and potentially provide relevant biological information about the sutural ossification processes to predict the onset of skull deformities and stratify post-surgical outcome., (© 2022. The Author(s).)

Purpose: To identify MRI-based quantitative craniofacial variables linked to airways narrowing and obstructive sleep apnea (OSA) development in children with achondroplasia., Methods: We evaluated skull base and midface MRI in two cohorts of children affected by achondroplasia, with (group 1) or without OSA (group 2). 3DFSPGR-T1weighted images were used to assess airways volume (nasopharynx, oropharynx, and laryngopharynx), jugular foramina (JF) and hypoglossal foramina (HF) areas, foramen magnum area, cervical cord area, and maxillary retrusion (SNA angle)., Results: Nineteen out of 27 children with achondroplasia exhibited different degrees of obstructive respiratory impairment (n.4 mild, n.8 moderate, n.7 severe), while 8 children did not show OSA. Each group was compared with age-matched controls without neuroimaging abnormalities. Both groups showed reduced nasopharynx volume, JF areas, and SNA angle, while group 1 showed also reduced oropharynx volume, ratio of FM/cervical cord areas, and HF areas (p < 0.05). A positive correlation between nasopharynx volume and SNA angle was found in both groups, while a positive correlation among upper airways volume, JF and HF areas was found only in group 1. No correlation between upper airways volume and OSA severity was found., Conclusion: In children with achondroplasia, multifaced craniofacial abnormalities contribute to airways volume reduction predisposing to sleep disordered breathing. MRI-based quantitative assessment allows the appraisal of craniofacial variables linked to the development of sleep-disordered breathing such as FM stenosis, jugular and hypoglossal foramina stenosis, and retruded maxillary position and may be a valuable tool for clinical surveillance., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)