Evaluation of Adult and Pediatric Chiari Type 1 Malformation Patients: Do Consensus Documents Fit Everyday Practice?

The management of Chiari 1 malformation (CM1) and Syringomyelia (Syr) has shown many changes in surgical indications and techniques over time. The dedicated neurosurgical and neurological community recently planned to analyze the state of the art and find conduct uniformity. This led to international consensus documents on diagnostic criteria and therapeutic strategies. We aimed to evaluate, in a large, monocentric surgical series of adult and children CM1 patients, if the daily clinical practice reflects the consensus documents. Our series comprises 190 pediatric and 220 adult Chiari patients submitted to surgery from 2000 to 2021. The main indications for the treatment were the presence of Syr and symptoms related to CM1. While there is great correspondence with the statements derived from the consensus documents about what to do for Syr and symptomatic CM1, the accordance is less evident in CM1 associated with craniosynostosis or hydrocephalus, especially when considering the early part of the series. However, we think that performing such studies could increase the homogeneity of surgical series, find a common way to evaluate long-term outcomes, and reinforce the comparability of different strategies adopted in different referral centers.

Chiari Malformation Type 1 and Syringomyelia: Why Do Patients Claim for International Guidelines? Commentary on the 2021 Chiari and Syringomyelia Consensus Document.

The diagnosis of Chiari malformation type 1 (CM1) and Syringomyelia (Syr) has become increasingly common during the past few years. Contemporarily, the body of literature on these topics is growing, although randomized controlled studies on significant case series to drive guidelines are missing in the pediatric and adult populations. As a result of the different opinions about surgical indications and techniques raised by CM1-Syr, an increasing number of well-informed but disoriented patients is emerging. To bridge this gap, an International Consensus Conference on CM1-Syr held in Milan in November 2019 aimed to find a consensus among international experts, to suggest some recommendations that, in the near future, could lead to guidelines. Here, we comment on the most relevant recommendations about the definition, diagnosis, surgical management, failures and re-intervention, and outcome. We also focus on some "wrong" indications or techniques that, although widely disapproved by the experts, and negatively experienced by many patients, are still largely in use.

Surface Cranial Ultrasound: The Natural Heir to X-Ray for the Screening of Skull Deformities in Infants.

PURPOSE: Volumetric tomography (3D-CT) is currently considered the gold standard for the diagnosis of craniosynostosis, but its use as the first-line examination for cranial deformities is a topic of debate, because of skull X-ray radiation and low sensitivity and specificity. Cranial ultrasound is an emerging noninvasive radiation-free alternative, but its diagnostic accuracy still needs confirmation. MATERIALS AND METHODS: The present prospective study included 350 infants with skull deformities, who underwent cranial ultrasound as the first-line examination, followed by 3D-CT if the echography results was positive or unclear. If the results were negative, infants underwent physical treatment and follow-up. To evaluate ultrasound reliability, we focused on cases that underwent both the index test and the gold standard and performed a double-blind comparison of the echography and 3D-CT results. RESULTS: Ultrasound documented patent sutures in 293 infants and 9 had inconclusive results. The 293 ultrasound-negative infants were followed clinically: all improved, except 28 that underwent 3D-CT. In all of these cases, 3D-CT confirmed the ultrasonography results (no false negatives). 48 infants showed premature suture closure and underwent 3D-CT: 47 were confirmed (true positive), 1 was false positive. The sensitivity was 100%, the specificity was 99.7%, the positive and negative predictive values were 97.9% and 100%, respectively, the accuracy was 99.7%, and the diagnostic test evaluation was conclusive. CONCLUSION: The study documented the high sensitivity and specificity of echography for the diagnosis of craniosynostosis in a referral center, with better results being achieved before 6 months of age. Major limitations are the loss of diagnostic significance as the child grows and the learning curve needed. The advantages are avoidance of radiation and chance to evaluate the brain at the same time.

Comparison between clinical evaluations and laboratory findings and the impact of biofilm on antimicrobial susceptibility in vitro in canine otitis externa.

BACKGROUND: In canine otitis externa (OE), biofilm-producing bacteria are frequently present but biofilm may be underdiagnosed clinically. HYPOTHESIS/OBJECTIVES: The study aimed to investigate an association between clinical and cytological findings with bacteriological data from dogs with OE, to establish, through Environmental Scanning Electron Microscope (ESEM) examination, whether the presence of biofilm in vivo can be predicted and to evaluate the impact of biofilm on antimicrobial susceptibility tests. MATERIALS AND METHODS: Fifty-six dogs showing clinical signs of OE were enrolled. One cotton swab each was collected for ESEM, bacterial culture and susceptibility testing and for cytology. Staphylococcus pseudintermedius (n = 42, 48.8%) and Pseudomonas aeruginosa (n = 26, 30.2%) were tested for their ability to form biofilm. Minimum Inhibitory Concentrations (MIC), Minimal Biofilm Inhibitory Concentrations (MBIC) and Minimal Biofilm Eradication Concentrations (MBEC) towards enrofloxacin, gentamicin, polymyxin B and rifampicin were determined. RESULTS: Pseudomonas aeruginosa was positively associated with the biofilm clinical evaluation (p < 0.01) and neutrophils (p < 0.05), nuclear streaks (p < 0.01) and rods bacteria (p < 0.01) on cytology. S. pseudintermedius was associated with a low presence of neutrophils. There was a statistical correlation between clinical and cytological biofilm presence (p ≤ 0.01), but none with the biofilm production assay nor ESEM biofilm detection. No differences were found comparing the results of MIC and MBIC. MBEC results showed higher values than MIC and MBIC for all antimicrobials tested (p ≤ 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: Biofilm presence in OE was often underdiagnosed. Even if there is no specific clinical or cytological pattern related to biofilm, its presence should always be suspected.

Could soluble minerals be hazardous to human health? Evidence from fibrous epsomite.

From a toxicological point of view, particulates and fibres with high solubility in water and/or in biological environments have not been considered in detail and the knowledge to date in this area is very scarce. In this study, the water-soluble natural epsomite fibres from Perticara Mine (Italy) were investigated using SEM-EDS, XRPD, ICP-AES and alpha spectrometry measurements which were combined and integrated to characterise the fibres' morphology, crystal chemistry and mineralogy. The morphological and morphometric results showed that most of the fibres are of inhalable size (Dae 5.09 µm) and can be potentially adsorbed from all parts of the respiratory tract. Chemical analysis reveals significant amounts of toxic elements (As, Co, Fe, Mn, Ni, Sr, Ti, Zn) and surprisingly high contents of radioactive isotopes (210Po and 228Th) in epsomite crystals, making the inhalation of these fibres potentially hazardous to human health. Through this study, we want to focus on soluble minerals, such as epsomite, which can be present in both natural and anthropic environments and have never been considered from the point of view of their potential hazard.

Diagnosis and treatment of Chiari malformation type 1 in children: the International Consensus Document.

BACKGROUND: Chiari malformation type 1 (CM1) is a rare condition where agreed classification and treatment are still missing. The goal of this study is to achieve a consensus on the diagnosis and treatment of CM1 in children. METHODS: A multidisciplinary panel formulated 57 provisional statements based on a review of the literature. Thirty-four international experts (IE) participated in a Delphi study by independently rating each statement on a 4-point Likert scale ("strongly disagree," "disagree," "agree," "strongly agree"). Statements that were endorsed ("agree" or "strongly agree") by < 75% of raters were re-formulated, or new statements were added, and another Delphi round followed (up to a maximum of three). RESULTS: Thirty-five IE were contacted and 34 agreed to participate. A consensus was reached on 30/57 statements (52.6%) after round 1. Three statements were added, and one removed. After round 2, agreement was reached on 56/59 statements (94.9%). Finally, after round 3, which took place during the 2019 Chiari Consensus Conference (Milan, Italy), agreement was reached on 58/59 statements (98.3%) about four main sections (Definition and Classification, Planning, Surgery, Isolated Syringomyelia). Only one statement did not gain a consensus, which is the "definition of radiological failure 24 month post-surgery." CONCLUSIONS: The consensus document consists of 58 statements (24 on diagnosis, 34 on treatment), serving clinicians and researchers following children with CM1. There is a clear need for establishing an international network and registry and to promote collaborative studies to increase the evidence base and optimize the long-term care of this patient population.

Diagnosis and treatment of Chiari malformation and syringomyelia in adults: international consensus document.

BACKGROUND: Syringomyelia and Chiari malformation are classified as rare diseases on Orphanet, but international guidelines on diagnostic criteria and case definition are missing. AIM OF THE STUDY: to reach a consensus among international experts on controversial issues in diagnosis and treatment of Chiari 1 malformation and syringomyelia in adults. METHODS: A multidisciplinary panel of the Chiari and Syringomyelia Consortium (4 neurosurgeons, 2 neurologists, 1 neuroradiologist, 1 pediatric neurologist) appointed an international Jury of experts to elaborate a consensus document. After an evidence-based review and further discussions, 63 draft statements grouped in 4 domains (definition and classification/planning/surgery/isolated syringomyelia) were formulated. A Jury of 32 experts in the field of diagnosis and treatment of Chiari and syringomyelia and patient representatives were invited to take part in a three-round Delphi process. The Jury received a structured questionnaire containing the 63 statements, each to be voted on a 4-point Likert-type scale and commented. Statements with agreement <75% were revised and entered round 2. Round 3 was face-to-face, during the Chiari Consensus Conference (Milan, November 2019). RESULTS: Thirty-one out of 32 Jury members (6 neurologists, 4 neuroradiologists, 19 neurosurgeons, and 2 patient association representatives) participated in the consensus. After round 2, a consensus was reached on 57/63 statements (90.5%). The six difficult statements were revised and voted in round 3, and the whole set of statements was further discussed and approved. CONCLUSIONS: The consensus document consists of 63 statements which benefited from expert discussion and fine-tuning, serving clinicians and researchers following adults with Chiari and syringomyelia.

A Multidisciplinary Approach in Examining the Susceptibility to Microbial Attack of Polyacrylic and Polyurethane Resins Used in Art Restoration.

The synthetic polymers used to protect artworks from deterioration process can be colonized by the fungi and bacteria responsible for the biodeterioration process. In this study, the susceptibility of synthetic polyacrylics and polyurethane resins to microorganisms (Aspergillus niger ATCC 9642, Aureobasidium pullulans ATCC 15233, Chaetomium globosum ATCC 6205, Cladosporium cladosporioides ATCC 16022, Alternaria alternata BC01, Penicillium citrinum LS1 and Pseudomonas aeruginosa ATCC 9027) was investigated. The microbial attack was simulated alone and with a biocide and the related growth was observed up to 21 days for bacteria and 28 days for fungi. The polyacrylic and polyurethane resins were subjected to microbial attack, regardless of the biocide treatment, with a fungal growth from 60% to the complete coverage of the plate surface. Penicillium citrinum showed the greatest adaptation ability and was found in all the examined resins. P. aeruginosa was visible in all the different resins, regardless of the presence of biocide. An environmental scanning electron microscope (ESEM) revealed the presence of fungal conidia and hyphae in the inoculated resins and the Fourier transform IR spectroscopy (FTIR-ATR) indicated chemical transformations in the IR spectra, particularly the hydrolysis of esters, with some differences between the polyacrylic and polyurethane resins, which were probably due to their different chemical features. Overall, our data stress that the chemical, physical and biological deterioration caused by microorganisms capable of degrading synthetic polymers is still a problem in art restoration and that new strategies must be considered to counteract this phenomenon.

The management of Chiari malformation type 1 and syringomyelia in children: a review of the literature.

In anticipation of the "Chiari and Syringomyelia Consensus Conference" held in Milan in 2019, we performed a systematic literature review on the management of Chiari malformation type 1 (CM1) and syringomyelia (Syr) in children.We aimed to summarize the available evidence and identify areas where consensus has not been reached and further research is needed.In accordance with PRISMA guidelines, we formulated seven questions in Patients-Interventions-Comparators-Outcomes (PICO) format. Six PICOs concerned CM1 children with/without additional structural anomalies (Syr, craniosynostosis, hydrocephalus, tethered cord, and cranio-vertebral junction anomalies), and one PICO Syr without CM1. We searched Medline, Embase, Cochrane, and NICE databases from January 1, 1999, to May 29, 2019. Cohort studies, controlled and randomized clinical trials (CCTs, RCTs), and systematic reviews were included, all pertinent only to patients ≤ 18 years of age.For CM1, 3787 records were found, 460 full texts were assessed and 49 studies (46 cohort studies, one RCT, and two systematic reviews) were finally included. For Syr, 376 records were found, 59 full texts were assessed, and five studies (one RCT and four cohort studies) were included. Data on each PICO were synthetized narratively due to heterogeneity in the inclusion criteria, outcome measures, and length of follow-up of the included studies.Despite decades of experience on CM1 and Syr management in children, the available evidence remains limited. Specifically, there is an urgent need for collaborative initiatives focusing on the adoption of shared inclusion criteria and outcome measures, as well as rigorous prospective designs, particularly RCTs.

Neuro-telehealth for fragile patients in a tertiary referral neurological institute during the COVID-19 pandemic in Milan, Lombardy.

BACKGROUND: Lombardy was severely hit by the COVID-19 pandemic since February 2020 and the Health System underwent rapid reorganization. Outpatient clinics were stopped for non-urgent patients: it became a priority to manage hundreds of fragile neurological patients who suddenly had less reference points. In Italy, before the pandemic, Televisits were neither recognized nor priced. METHODS: At the Fondazione IRCCS Istituto Neurologico C. Besta, we reorganized outpatient clinics to deliver Neuro-telemedicine services, including Televisits and Teleneurorehabilitation, since March 2020. A dedicated Working Group prepared the procedure, tested the system, and designed satisfaction questionnaires for adults and children. RESULTS: After a pilot phase, we prepared a procedure for Telemedicine outpatient clinics which was approved by hospital directions. It included prescription, booking, consenting, privacy and data protection, secure connection with patients (Teams Microsoft 365), electronic report preparation and delivery, reporting, and accountability of the services. During the March-September 2020 period, we delivered 3167 Telemedicine services, including 1618 Televisits, to 1694 patients (972 adults, 722 children) with a wide range of chronic neurological disorders. We successfully administered different clinical assessment and scales. Satisfaction among patients and caregivers was very high. CONCLUSIONS: During the dramatic emergency, we were able to take care of more than 1600 patients by organizing Neuro-telehealth in a few weeks, lessening the impact of the pandemic on fragile patients with chronic neurological disorders; this strategy is now stably embedded in our care pathways. In Italy, Telehealth is at present recognized and priced and is becoming a stable pillar of the health system.

Early de-tethering: analysis of urological and clinical consequences in a series of 40 children.

PURPOSE: Early de-tethering procedures are performed on spinal dysraphisms to prevent neuro-urological deterioration caused by growth. Partial lipoma removal may cause delayed deterioration by re-tethering, while complete removal may increase the risk of postoperative worsening. The present study evaluates the risk of postoperative deterioration and the protective potential of intraoperative neurophysiological monitoring (IOM), with a special reference to the conus lipomas treated with the radical approach. METHODS: Forty toddlers (< 24 months) underwent complete perioperative neurological and urological assessment, including urodynamic study (UDS). The dysraphisms were subgrouped according to Pang's classification. IOM was applied in all patients: transcranial motor evoked potentials (tMep) combined with mapping were recorded in all cases while bulbocavernosus reflex (BCR) was evaluable just in 7 cases. RESULTS: At preoperative evaluation, 11 children already had UDS impairment and 2 had motor disturbances before neurosurgery. At 1-month follow-up, preoperative motor disturbances were stable, 7/11 UDS alterations normalized, and the remaining 4 were stable. At 6-month follow-up, all motor deficits and 8/11 preoperative UDS alterations had improved. Unfortunately, 7 children with previously normal UDS experienced a new impairment after surgery: 2/7 normalized while 5/7 did not recover. This postoperative permanent urodynamic impairment occurred in 4 chaotic lipoma (CLchaos) and in one terminal myelocystocele (TMC) that means a surgical deterioration rate of 22% for the high risk cases. CONCLUSIONS: This small highly selected series confirms that early de-tethering may stop or revert the spontaneous neuro-urological deterioration: in fact, preoperative UDS impairment was frequent (27.5%) and improved in all the low surgical risk cases (limited dorsal myeloschisis, filar, transitional and dorsal lipomas). On the contrary, in CLchaos and TMC, early de-tethering was unable to revert preoperative UDS impairment, and radical surgery carried a high risk of new neuro-urological deterioration directly caused by the operation. In our experience, IOM had a protective role for motor functions, while it was less effective for the neuro-urological ones, probably due to the anesthesiology regimens applied. In conclusion, among the dysraphisms, CLchoas proved to be the worst enemy that often camouflages at MRI. Affording it without all possible IOM weapons carries a high risk to harm the patient.

Chiari 1 malformation and untreated sagittal synostosis: a new subset of complex Chiari?

PURPOSE: Chiari 1 malformation (CM1) is a well-known association with complex craniosynostosis (CC), while it has been rarely reported in association with monosynostosis. The aim of the present study is to investigate on the association between CM1 and untreated sagittal synostosis (USS). METHOD: The study included 48 cases of sagittal synostosis (SS), untreated for misdiagnosis and associated with CM1. The children were firstly diagnosed for CM1 by MRI (mean age 9) than for SS (mean age 10.5) by three-dimensional computerized tomography (3D-CT), which documented the absence of the sagittal suture, in the presence of residual indentation of all the other sutures. Syndromic cases were diagnosed by clinical evaluation and molecular studies. RESULTS: Of the 48 children harboring CM1 plus USS, 21 were asymptomatic for CM1 and are still on follow-up, while 27 children were operated for syringomyelia and scoliosis and/or occurrence of symptoms, three of them had an acute presentation (two papilledema and one sleep apneas) and 11 children had a documented increase of preoperative ICP. Craniovertebral decompression (CVD) was the first-line surgery in 24 children, 16 with duroplasty and five without and eight had also cerebellar (CBL) tonsil coagulation. A cranial vault remodelling was firstly performed in three children. Fifteen percent of children submitted to CVD needed a revision for cerebrospinal fluid (CSF) collection, while two needed both the supra- and infratentorial decompressive procedure and another two needed a treatment for the associated hydrocephalus. CONCLUSIONS: The present study identified an USS in 27 (15.5%) of 174 CM1 children operated for a symptomatic CM1. We suggest to define this association CM1 plus USS, a new subtype of complex CM1. For the high percentage of complications and multiple procedures needed to solve the CM1, we advise to identify by 3D-CT scan these children before performing CVD. Our finding suggests also that, if left untreated, SS may lead to the delayed occurrence of a challenging subset of CM1.

Chiari I malformation in defined genetic syndromes in children: are there common pathways?

PURPOSE: Chiari malformation type I (CMI) is a common pediatric neurologic anomaly that can be associated with a variety of genetic disorders; however, it is not always clear whether the observed associations are real or random. The knowledge of the real associations could provide useful guidance to clinicians. Furthermore, it could be of help to better understand the still unknown genetic etiology of CMI. METHODS: With the aim of implementing such insights, we retrospectively reviewed clinical, neuroradiological, and genetic data of patients harboring CMI evaluated at the Child Neurology Unit of our institution between January 2008 and December 2018. RESULTS: The cohort consists of 205 patients (111 males and 94 females), with a mean age at diagnosis of 6.3 years (range 0-18 years). 188 patients completed an average follow-up period of 5.2 years (range one month-18 years). Mean age at last assessment was 11.4 years (range nine months-23 years). 127 (62%) children have been classified as syndromic due to the presence of neurodevelopmental disorders, phenotypic anomalies, or malformations. Among syndromic CMI children, a molecular diagnosis was identified in 35/127 (27.6%) (20 males and 15 females). The most common diagnoses were syndromic craniosynostosis in 8/35 children (22.9%), among which sevenare FGFR-related and one ERF-related craniosynostosis; disorders of the RAS/MAPK pathway, termed RASopathies or RAS/MAPK syndromes in 9/35 (25.7%); disorders of the PTEN-PI3K/AKT signal transduction cascade, termed PTENopathies in 3/35 children (8.6%); and chromosomal rearrangements in 6/35 patients (17.1%), two of whom with del16p11.2. CONCLUSIONS: We polarized our attention on the defined genetic diagnoses focusing not only on the phenotypic hallmarks but also on the phenotypic overlapping features. In addition, we discussed the pathophysiological mechanisms leading to progressive cerebellar ectopia and the involved molecular pathways. Along with the recent literature evidence, we suppose that interactions between FGFR and RAS/MAPK pathway and between RAS/MAPK and PTEN-PI3K/AKT pathways could explain some phenotypic overlapping features and could have a significant role in the pathogenesis of CMI.

Geological occurrence, mineralogical characterization, and risk assessment of potentially carcinogenic erionite in Italy.

Erionite is a zeolite representing a well-known health hazard. In fact, exposure of humans to its fibers has been unequivocally associated with occurrence of malignant mesothelioma. For this reason, a multi-methodological approach, based upon field investigation, morphological characterization, scanning electron microscopy (SEM)/energy-dispersive spectroscopy (EDS) chemical analysis, and structure refinement through X-ray powder diffraction (XRPD), was applied to different samples of potentially carcinogenic erionite from Northern Italy. The studied crystals have a chemical composition ranging from erionite-Ca to erionite-Na and display variable morphologies, varying from prismatic, through acicular and fibrous, to extremely fibrous asbestiform habits. The fibrous samples were characterized by an unusual preferred partition of aluminum (Al) at tetrahedral site T1 instead of tetrahedral site T2. Further, a mismatch between the a-parameter of erionite-Ca and levyne-Ca that are intergrown in the asbestiform sample was detected. This misfit was coupled to a relevant micro-strain to maintain structure coherency at the boundary. Erionite occurs in 65% of the investigated sites, with an estimated quantity of 10 to 40 vol% of the associated minerals. The presence of this mineral is of concern for risk to human health, especially if one considers the vast number of quarries and mining-related activities that are operating in the zeolite host rocks. The discovery of fibrous and asbestiform erionite in Northern Italy suggests the need for a detailed risk assessment in all Italian areas showing the same potential hazard, with specific studies such as a quantification of the potentially respirable airborne fibers and targeted epidemiological surveillance.

Chiari malformation-related headache: outcome after surgical treatment.

The outcome of headache in a series of 135 operated CM1 is presented. Favorable results were obtained in 85% of atypical and 93% typical headache with the support of a multidisciplinary approach that restricted the indications for surgery.

Discrete or diffuse intramedullary tumor? Contrast-enhanced intraoperative ultrasound in a case of intramedullary cervicothoracic hemangioblastomas mimicking a diffuse infiltrative glioma: technical note and case report.

Hemangioblastomas are benign, highly vascularized intramedullary lesions that may also extend into the intradural space. Surgery represents the standard therapy, with the goal of obtaining complete resection even at the risk of neurological morbidity. MRI is the gold standard for diagnosis and assessment of intramedullary tumors. Nevertheless, sometimes MRI may not accurately differentiate between different types of intramedullary tumors, in particular if they are associated with syringes or intra- and peritumoral cysts. This could subsequently affect surgical strategies. Intraoperative ultrasound (ioUS) has become in the last few years a very useful tool for use during neurosurgical procedures. Various ioUS modalities such as B-mode and Doppler have been applied during neurosurgical procedures. On the other hand, the use of contrast-enhanced ultrasound (CEUS) is not yet well defined and standardized in this field. We report a case of a young patient harboring a cervicothoracic intramedullary tumor, for which the preoperative neuroradiologi-cal diagnosis was in favor of a diffuse astrocytoma with nodular components whereas ioUS demonstrated 3 distinct intramedullary nodules. CEUS showed highly vascularized lesions, compatible with hemangioblastomas. These findings, particularly those obtained with CEUS, allowed better definition of the lesions for diagnosis, enhanced understanding of the physiopathological aspects, and permitted the localization of all 3 nodules, thus limiting spinal cord manipulation and allowing complete resection of the lesions, with an uneventful postoperative neurological course. To the best of our knowledge, this is the first report of the use of intraoperative CEUS in a case of intramedullary hemangioblastoma.

The in vitro cytotoxic effects of natural (fibrous epsomite crystals) and synthetic (Epsom salt) magnesium sulfate.

Exposure to mineral fibers represents an occupational and environmental hazard since particulate inhalation leads to several health disorders. However, few data are available on the effect of fibers with high solubility like natural epsomite, a water-soluble fiber with an inhalable size that allows it to penetrate biological systems, with regard to the respiratory tract. This study evaluated the natural (fibrous epsomite) and synthetic (Epsom salt) magnesium sulfate pathogenicity. Investigations have been performed through morpho-functional and biochemical analyses, in an in vitro cell model that usually grows as monocytes, but that under appropriate conditions differentiates into macrophages. These latter, known as alveolar macrophages, if referred to lungs, represent the first line of defense against harmful inhaled stimuli. Morphological observations reveal that, if Epsom salt induces osmotic stress on cell culture, natural epsomite fibers lead to cellular alterations including thickening of the nuclear envelope and degenerated mitochondria. Moreover, the insoluble fraction (impurities) internalized by cells induces diffuse damage characterized at the highest dosage and exposure time by secondary necrosis or necrotic cell death features. Biochemical analyses confirm this mineral behavior that involves MAPK pathway activation, resulting in many different cellular responses ranging from proliferation control to cell death. Epsom salt leads to MAPK/ERK activation, a marker predictive of overall survival. Unlike, natural epsomite induces upregulation of MAPK/p38 protein involved in the phosphorylation of downstream targets driving necrotic cell death. These findings demonstrate natural epsomite toxicity on U937 cell culture, making the inhalation of these fibers potentially hazardous for human health. RESEARCH HIGHLIGHTS: Natural epsomite and synthetic Epsom salt effects have been evaluated in U937 cell model. Epsom salt induces an osmotic cellular stress. Natural epsomite fibers lead to cellular damage and can be considered potentially dangerous for human health.

Surgical Management of Chiari 1.5 in Children: A Truly Different Disease?

Background: In patients with Chiari 1.5 malformation (CM1.5), a more aggressive disease course and an increased association with craniovertebral junction (CVJ) anomalies has been suggested. The best management of this subgroup of patients is not clearly defined, also due to the lack of specific series elucidating this anomaly's peculiar characteristics. Methods: We evaluated a series of 33 patients (25 females, 8 males; mean age at surgery: 13 years) fulfilling the criteria for Chiari 1.5 diagnosis who underwent posterior fossa decompression and duraplasty (PFDD) between 2006 and 2021. Results: Headache was present in all children, five presented central apnea, five had dysphagia, and three had rhinolalia. Syringomyelia was present in 19 (58%) children. Twenty patients (61%) showed various CVJ anomalies, but only one child presented instability requiring arthrodesis. The mean tonsil displacement below the foramen magnum was 19.9 mm (range: 12-30), without significant correlation with the severity of symptoms. Syringomyelia recurred or was unchanged in three patients, and one needed C1-C2 fixation. The headache disappeared in 28 children (84%). Arachnoid opening and tonsil coagulation or resection was necessary for 19 children (58%). Conclusions: In our pediatric CM series, the need for tonsil resection or coagulation was higher in CM1.5 children due to a more severe crowding.