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1. CRISIS AFAR: an international collaborative study of the impact of the COVID-19 pandemic on mental health and service access in youth with autism and neurodevelopmental conditions

Author

Bethany Vibert, Patricia Segura, Louise Gallagher, Stelios Georgiades, Panagiota Pervanidou, Audrey Thurm, Lindsay Alexander, Evdokia Anagnostou, Yuta Aoki, Catherine S. Birken, Somer L. Bishop, Jessica Boi, Carmela Bravaccio, Helena Brentani, Paola Canevini, Alessandra Carta, Alice Charach, Antonella Costantino, Katherine T. Cost, Elaine A Cravo, Jennifer Crosbie, Chiara Davico, Federica Donno, Junya Fujino, Alessandra Gabellone, Cristiane T Geyer, Tomoya Hirota, Stephen Kanne, Makiko Kawashima, Elizabeth Kelley, Hosanna Kim, Young Shin Kim, So Hyun Kim, Daphne J. Korczak, Meng-Chuan Lai, Lucia Margari, Lucia Marzulli, Gabriele Masi, Luigi Mazzone, Jane McGrath, Suneeta Monga, Paola Morosini, Shinichiro Nakajima, Antonio Narzisi, Rob Nicolson, Aki Nikolaidis, Yoshihiro Noda, Kerri Nowell, Miriam Polizzi, Joana Portolese, Maria Pia Riccio, Manabu Saito, Ida Schwartz, Anish K. Simhal, Martina Siracusano, Stefano Sotgiu, Jacob Stroud, Fernando Sumiya, Yoshiyuki Tachibana, Nicole Takahashi, Riina Takahashi, Hiroki Tamon, Raffaella Tancredi, Benedetto Vitiello, Alessandro Zuddas, Bennett Leventhal, Kathleen Merikangas, Michael P. Milham, and Adriana Di Martino

Subjects
Mental health outcomes, Autism spectrum disorder, Neurodevelopmental conditions, Sleep, Behavioral problems, Prediction, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Heterogeneous mental health outcomes during the COVID-19 pandemic are documented in the general population. Such heterogeneity has not been systematically assessed in youth with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). To identify distinct patterns of the pandemic impact and their predictors in ASD/NDD youth, we focused on pandemic-related changes in symptoms and access to services. Methods Using a naturalistic observational design, we assessed parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) Adapted For Autism and Related neurodevelopmental conditions (AFAR). Cross-sectional AFAR data were aggregated across 14 European and North American sites yielding a clinically well-characterized sample of N = 1275 individuals with ASD/NDD (age = 11.0 ± 3.6 years; n females = 277). To identify subgroups with differential outcomes, we applied hierarchical clustering across eleven variables measuring changes in symptoms and access to services. Then, random forest classification assessed the importance of socio-demographics, pre-pandemic service rates, clinical severity of ASD-associated symptoms, and COVID-19 pandemic experiences/environments in predicting the outcome subgroups. Results Clustering revealed four subgroups. One subgroup—broad symptom worsening only (20%)—included youth with worsening across a range of symptoms but with service disruptions similar to the average of the aggregate sample. The other three subgroups were, relatively, clinically stable but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Distinct combinations of a set of pre-pandemic services, pandemic environment (e.g., COVID-19 new cases, restrictions), experiences (e.g., COVID-19 Worries), and age predicted each outcome subgroup. Limitations Notable limitations of the study are its cross-sectional nature and focus on the first six months of the pandemic. Conclusions Concomitantly assessing variation in changes of symptoms and service access during the first phase of the pandemic revealed differential outcome profiles in ASD/NDD youth. Subgroups were characterized by distinct prediction patterns across a set of pre- and pandemic-related experiences/contexts. Results may inform recovery efforts and preparedness in future crises; they also underscore the critical value of international data-sharing and collaborations to address the needs of those most vulnerable in times of crisis.

Published
2023
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2. Brain perivascular spaces and autism: clinical and pathogenic implications from an innovative volumetric MRI study

Author

Maria Alessandra Sotgiu, Alessandro Lo Jacono, Giuseppe Barisano, Laura Saderi, Vanna Cavassa, Andrea Montella, Paola Crivelli, Alessandra Carta, and Stefano Sotgiu

Subjects
autism, glymphatic system, perivascular spaces, Virchow-Robin spaces, MRI, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

IntroductionOur single-center case–control study aimed to evaluate the unclear glymphatic system alteration in autism spectrum disorder (ASD) through an innovative neuroimaging tool which allows to segment and quantify perivascular spaces in the white matter (WM-PVS) with filtering of non-structured noise and increase of the contrast-ratio between perivascular spaces and the surrounding parenchyma.MethodsBriefly, files of 65 ASD and 71 control patients were studied. We considered: ASD type, diagnosis and severity level and comorbidities (i.e., intellectual disability, attention-deficit hyperactivity disorder, epilepsy, sleep disturbances). We also examined diagnoses other than ASD and their associated comorbidities in the control group.ResultsWhen males and females with ASD are included together, WM-PVS grade and WM-PVS volume do not significantly differ between the ASD group and the control group overall. We found, instead, that WM-PVS volume is significantly associated with male sex: males had higher WM-PVS volume compared to females (p = 0.01). WM-PVS dilation is also non-significantly associated with ASD severity and younger age (< 4 years). In ASD patients, higher WM-PVS volume was related with insomnia whereas no relation was found with epilepsy or IQ.DiscussionWe concluded that WM-PVS dilation can be a neuroimaging feature of male ASD patients, particularly the youngest and most severe ones, which may rely on male-specific risk factors acting early during neurodevelopment, such as a transient excess of extra-axial CSF volume. Our findings can corroborate the well-known strong male epidemiological preponderance of autism worldwide.

Published
2023
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3. The Role of SNAP-25 in Autism Spectrum Disorders Onset Patterns

Author

Elisabetta Bolognesi, Franca Rosa Guerini, Alessandra Carta, Matteo Chiappedi, Stefano Sotgiu, Martina Maria Mensi, Cristina Agliardi, Milena Zanzottera, and Mario Clerici

Subjects
autism spectrum disorders (ASD), ASD classic onset, ASD regressive onset, SNAP-25 gene (synaptosomal-associated protein of 25 kDa), regression, epigenetics, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Autism spectrum disorders (ASD) can present with different onset and timing of symptom development; children may manifest symptoms early in their first year of life, i.e., early onset (EO-ASD), or may lose already achieved skills during their second year of life, thus showing a regressive-type onset (RO-ASD). It is still controversial whether regression represents a neurobiological subtype of ASD, resulting from distinct genetic and environmental causes. We focused this study on the 25 kD synaptosomal-associated protein (SNAP-25) gene involved in both post-synaptic formation and adhesion and considered a key player in the pathogenesis of ASD. To this end, four single nucleotide polymorphisms (SNPs) of the SNAP-25 gene, rs363050, rs363039, rs363043, and rs1051312, already known to be involved in neurodevelopmental and psychiatric disorders, were analyzed in a cohort of 69 children with EO-ASD and 58 children with RO-ASD. Both the rs363039 G allele and GG genotype were significantly more frequently carried by patients with EO-ASD than those with RO-ASD and healthy controls (HC). On the contrary, the rs1051312 T allele and TT genotype were more frequent in individuals with RO-ASD than those with EO-ASD and HC. Thus, two different SNAP-25 alleles/genotypes seem to discriminate between EO-ASD and RO-ASD. Notably, rs1051312 is located in the 3′ untranslated region (UTR) of the gene and is the target of microRNA (miRNA) regulation, suggesting a possible epigenetic role in the onset of regressive autism. These SNPs, by discriminating two different onset patterns, may represent diagnostic biomarkers of ASD and may provide insight into the different biological mechanisms towards the development of better tailored therapeutic and rehabilitative approaches.

Published
2023
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4. Occurrence of hyperventilation-induced high amplitude rhythmic slowing with altered awareness after successful treatment of typical absence seizures and a network hypothesis

Author

Simone Mattozzi, Caterina Cerminara, Maria A. Sotgiu, Alessandra Carta, Antonella Coniglio, Denis Roberto, Delia M. Simula, Gian Luca Pruneddu, Silvia Dell'Avvento, S. Sonia Muzzu, Maria Fadda, Giovanni M. Luzzu, Stefano Sotgiu, and Susanna Casellato

Subjects
HIHARS, Loss of awareness, Typical absence, Hyperventilation, Alkalosis, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Background: Typical absence seizures (AS) are epileptic phenomena typically appearing in children 4–15 years of age and can be elicited by hyperventilation (HV). Hyperventilation-induced high-amplitude rhythmic slowing (HIHARS) represents a paraphysiological response during HV and may manifest with alteration of awareness (HIHARSAA). To date, HIHARSAA has mostly been described in patients without epilepsy. Aim: To describe five patients with treatment-responsive typical AS who, after becoming seizure free, presented with HIHARSAA. Methods: By using video-electroencephalographic recording (Video-EEG), we describe differential clinical characteristics and ictal electrophysiological patterns of both typical AS and HIHARSAA. Results: We demonstrate that when HIHARSAA occurs in patients with typical AS there is a temporal window between the two phenomena. This suggests that the presence of typical AS precludes the appearance of HIHARSAA. Conclusions: We hypothesize that alkalosis and dysfunction of the same neural network are involved in both typical AS and HIHARSAA and that their distinct electroclinic manifestations are due to the involvement of different ion channels. Significance: A better understanding of the characteristics of typical AS and HIHARSAA and of the role of alkalosis in both, can help avoiding misdiagnosis and identifying more suitable therapies for typical AS.

Published
2021
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5. Temperament Dimensions and Awakening Cortisol Levels in Attention-Deficit/Hyperactivity Disorder

Author

Alessandra Carta, Isabella Vainieri, Anna-Sophie Rommel, Alessandro Zuddas, Jonna Kuntsi, Stefano Sotgiu, and Nicoletta Adamo

Subjects
ADHD, temperament, cortisol, arousal, biomarkers, Psychiatry, RC435-571
Abstract

ObjectiveTo investigate whether temperament dimensions, Effortful Control (EC), Surgency-Extraversion (SE), and Negative Affectivity (NA), are associated with attention-deficit/hyperactivity disorder (ADHD) and how they relate to awakening cortisol levels, as a proxy measure of peripheral arousal.MethodsParent-rated temperament and saliva samples were collected from 55 children with ADHD and 65 age-matched controls.ResultsCompared to controls, youths with ADHD showed lower EC, higher NA, and lower awakening cortisol levels but did not differ in SE. Similar findings emerged in dimensional analyses linking temperament traits to inattention and hyperactivity-impulsivity symptoms. The results remained unchanged when controlling for the presence of co-occurring opposition-defiance and anxiety traits, as well as medication status. Temperament dimensions were not associated with cortisol levels.ConclusionsPoor temperamental emotional and cognitive self-regulation showed significant associations with ADHD but did not appear to be linked to the under-arousal typically seen in ADHD.

Published
2022
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6. GC1f Vitamin D Binding Protein Isoform as a Marker of Severity in Autism Spectrum Disorders

Author

Elisabetta Bolognesi, Franca Rosa Guerini, Stefano Sotgiu, Matteo Chiappedi, Alessandra Carta, Martina Maria Mensi, Cristina Agliardi, Milena Zanzottera, and Mario Clerici

Subjects
autism spectrum disorders (ASD), vitamin D binding protein (DBP), GC isoforms, pathogenesis, clinical severity, Nutrition. Foods and food supply, TX341-641
Abstract

Autism spectrum disorders (ASD) are characterized by a wide spectrum of clinical, behavioral, and cognitive manifestations. It is, therefore, crucial to investigate possible biomarkers associated with specific ASD phenotypes. Ample literature suggests a possible role for vitamin D (VD) in influencing ASD clinical phenotypes. We analyzed three vitamin D binding protein gene (DBP) functional polymorphisms (rs2282679, rs7041, and rs4588), which are involved in the modulation of vitamin D serum concentration in 309 ASD children and 831 healthy controls. Frequency comparisons of single nucleotide polymorphisms (SNPs) alleles, genotypes, and GC isoforms (GC1f, G1s, and GC2)—generated by the combination of rs7041 and rs4588 alleles—were correlated with ASD diagnostic, behavioral, and functioning scales. The GC1f isoform was significantly more frequent in ASD compared with controls (18.6% vs. 14.5% pc = 0.02). Significantly higher scores for item 15 of the Childhood Autism Rating Scale (CARS) and lower ones for the Children’s Global Assessment Scale (CGAS) functioning scales were seen in ASD carrying the GC1f isoform. In GC phenotype analysis, a gradient of severity for overall CARS scores and CARS item 15 was observed, with scores decreasing according to the presence of GC1f-GC1f > GC1f-GC1s > GC1s-GC1s > GC1f-GC2 > GC2-GC2 isoforms. Similarly, lower CGAS scores were seen in carriers of the GC1f-GC1f isoform, whereas higher scores were present in those carrying GC2-GC2 (p = 0.028). This is the first study to evaluate possible relationships between GC variants and the different aspects of ASD in Italian ASD children. Results, although needing to be validated in ampler cohorts, suggest that the GC1f isoform could be a marker of severity in ASD that may be useful in establishing the intensity of therapeutic and rehabilitative protocols.

Published
2022
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7. VARS2-linked mitochondrial encephalopathy: two case reports enlarging the clinical phenotype

Author

Chiara Begliuomini, Giorgio Magli, Maja Di Rocco, Filippo M. Santorelli, Denise Cassandrini, Claudia Nesti, Federica Deodato, Daria Diodato, Susanna Casellato, Delia M. Simula, Veronica Dessì, Anna Eusebi, Alessandra Carta, and Stefano Sotgiu

Subjects
Mitochondrial disorder, Epileptic encephalopathy, Developmental delay, VARS2, Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background Mitochondrial respiratory chain consists of five complexes encoded by nuclear and mitochondrial genomes. Mitochondrial aminoacyl-tRNA synthetases are key enzymes in the synthesis of such complexes. Bi-allelic variants of VARS2, a nuclear gene encoding for valyl-tRNA (Val-tRNA) synthetase, are associated to several forms of mitochondrial encephalopathies or cardiomyoencephalopathies. Among these, the rare homozygous c.1100C > T (p.Thr367Ile) mutation variably presents with progressive developmental delay, axial hypotonia, limbs spasticity, drug-resistant epilepsy leading, in some cases, to premature death. Yet only six cases, of which three are siblings, harbouring this homozygous mutation have been described worldwide. Case presentation Hereby, we report two additional cases of two non-related young girls from Sardinia, born from non-consanguineous and healthy parents, carrying the aforesaid homozygous VARS2 variant. At onset both the patients presented with worsening psychomotor delay, muscle hypotonia and brisk tendon reflexes. Standard genetic tests were normal, as well as metabolic investigations. Brain MRI showed unspecific progressive abnormalities, such as corpus callosum hypoplasia (patient A) and cerebellar atrophy (patient A and B). Diagnosis was reached by adopting massive parallel next generation sequencing. Notably clinical phenotype of the first patient appears to be milder compared to previous known cases. The second patient eventually developed refractory epilepsy and currently presents with severe global impairment. Because no specific treatment is available as yet, both patients are treated with supporting antioxidant compounds along with symptomatic therapies. Conclusions Given the paucity of clinical data about this very rare mitochondrial encephalopathy, our report might contribute to broaden the phenotypic spectrum of the disorder. Moreover, noteworthy, three out of five pedigrees so far described belong to the Northern Sardinia ethnicity.

Published
2019
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8. Antihuman Endogenous Retrovirus Immune Response and Adaptive Dysfunction in Autism

Author

Alessandra Carta, Maria Antonietta Manca, Chiara Scoppola, Elena Rita Simula, Marta Noli, Stefano Ruberto, Marta Conti, Ignazio Roberto Zarbo, Roberto Antonucci, Leonardo A. Sechi, and Stefano Sotgiu

Subjects
human endogenous retroviruses, autism spectrum disorders, immune response, antibodies, adaptive behaviour, Biology (General), QH301-705.5
Abstract

ASD is a neurodevelopmental disorder of unknown aetiology but with a known contribution of pathogenic immune-mediated mechanisms. HERVs are associated with several neuropsychiatric diseases, including ASD. We studied anti-HERV-W, -K and -H-env immune profiles in ASD children to analyse differences between their respective mothers and child/mother control pairs and possible correlations to ASD severity and loss of adaptive abilities. Of the 84 studied individuals, 42 children (23 ASD and 19 neurotypical) and their paired mothers underwent clinical and neuropsychological evaluations. ASD severity was analysed with standardised tests. Adaptive functioning was studied with ABAS-II and GAC index. Plasma anti-env responses of HERV-K, -H and -W were tested with indirect ELISA. ASD and neurotypical children did not differ in age, gender, comorbidities and anti-HERV responses. In children with ASD, anti-HERV levels were not correlated to ASD severity, while a significant inverse correlation was found between anti-HERV-W-248-262 levels and adaptive/social abilities. Upregulation of anti-HERV-W response correlates to dysfunctional social and adaptive competences in ASD but not in controls, suggesting anti-HERV response plays a role in the appearance of peculiar ASD symptoms.

Published
2022
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9. Metabolomic Characterization of Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)

Author

Federica Murgia, Antonella Gagliano, Marcello G. Tanca, Noga Or-Geva, Aran Hendren, Sara Carucci, Manuela Pintor, Francesca Cera, Fausto Cossu, Stefano Sotgiu, Luigi Atzori, and Alessandro Zuddas

Subjects
metabolomics, pediatric acute-onset neuropsychiatric syndrome, neuroinflammation, oxidative stress, biomarkers, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

IntroductionPANS is a controversial clinical entity, consisting of a complex constellation of psychiatric symptoms, adventitious changes, and expression of various serological alterations, likely sustained by an autoimmune/inflammatory disease. Detection of novel biomarkers of PANS is highly desirable for both diagnostic and therapeutic management of affected patients. Analysis of metabolites has proven useful in detecting biomarkers for other neuroimmune-psychiatric diseases. Here, we utilize the metabolomics approach to determine whether it is possible to define a specific metabolic pattern in patients affected by PANS compared to healthy subjects.DesignThis observational case-control study tested consecutive patients referred for PANS between June 2019 to May 2020. A PANS diagnosis was confirmed according to the PANS working criteria (National Institute of Mental Health [NIMH], 2010). Healthy age and sex-matched subjects were recruited as controls.MethodsThirty-four outpatients referred for PANS (mean age 9.5 years; SD 2.9, 71% male) and 25 neurotypical subjects matched for age and gender, were subjected to metabolite analysis. Serum samples were obtained from each participant and were analyzed using Nuclear Magnetic Resonance (NMR) spectroscopy. Subsequently, multivariate and univariate statistical analyses and Receiver Operator Curves (ROC) were performed.ResultsSeparation of the samples, in line with the presence of PANS diagnosis, was observed by applying a supervised model (R2X = 0.44, R2Y = 0.54, Q2 = 0.44, p-value < 0.0001). The significantly altered variables were 2-Hydroxybutyrate, glycine, glutamine, histidine, tryptophan. Pathway analysis indicated that phenylalanine, tyrosine, and tryptophan metabolism, as well as glutamine and glutamate metabolism, exhibited the largest deviations from neurotypical controls.ConclusionWe found a unique plasma metabolic profile in PANS patients, significantly differing from that of healthy children, that suggests the involvement of specific patterns of neurotransmission (tryptophan, glycine, histamine/histidine) as well as a more general state of neuroinflammation and oxidative stress (glutamine, 2-Hydroxybutyrate, and tryptophan-kynurenine pathway) in the disorder. This metabolomics study offers new insights into biological mechanisms underpinning the disorder and supports research of other potential biomarkers implicated in PANS.

Published
2021
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10. CACNA1A-Linked Hemiplegic Migraine in GLUT 1 Deficiency Syndrome: A Case Report

Author

Chiara Scoppola, Giorgio Magli, Marta Conti, Maria Fadda, Giovanni M. Luzzu, Delia M. Simula, Alessandra Carta, Stefano Sotgiu, and Susanna Casellato

Subjects
GLUT1 deficiency syndrome, hemiplegic migraine, CACNA1A, epilepsy, headache, SLC2A1, Neurology. Diseases of the nervous system, RC346-429
Abstract

Background: Glucose-transporter-1 deficiency syndrome (GLUT1-DS), due to SLC2A1 gene mutation, is characterized by early-onset seizures, which are often drug-resistant, developmental delay, and hypotonia. Hemiplegic migraine (HM) is a rare form of migraine, defined by headache associated with transient hemiplegia, and can be caused by mutations in either CACNA1A, ATP1A2, or SCN1A. Paroxysmal movements, other transient neurological disorders, or hemiplegic events can occur in GLUT1-DS patients with a mild phenotype.Case: We report on a girl with GLUT1-DS, due to SLC2A1 mutation, with a mild phenotype. In early childhood, she developed epilepsy and mild cognitive impairment, balance disorders, and clumsiness. At the age of 9, the patient reported a first hemiplegic episode, which regressed spontaneously. Over the next 3 years, two similar episodes occurred, accompanied by headache. Therefore, in the hypothesis of HM, genetic testing was performed and CACNA1A mutation was identified. The treatment with Lamotrigine avoided the recurrence of HM episodes.Discussion: To our knowledge, among the several cases of GLUT1-DS with HM symptoms described in the literature, genetic testing was only performed in two of them, which eventually proved to be negative. In all other cases, no other genes except for SLC2A1 were examined. Consequently, our patient would be the first description of GLUT1-DS with HM due to CACNA1A mutation. We would emphasize the importance of performing specific genetic testing in patients with GLUT1-DS with symptoms evocative of HM, which may allow clinicians to use specific pharmacotherapy.

Published
2021
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11. Clinical and Neurobehavioral Features of Three Novel Kabuki Syndrome Patients with Mosaic KMT2D Mutations and a Review of Literature

Author

Francesca Romana Lepri, Dario Cocciadiferro, Bartolomeo Augello, Paolo Alfieri, Valentina Pes, Alessandra Vancini, Cristina Caciolo, Gabriella Maria Squeo, Natascia Malerba, Iolanda Adipietro, Antonio Novelli, Stefano Sotgiu, Renzo Gherardi, Maria Cristina Digilio, Bruno Dallapiccola, and Giuseppe Merla

Subjects
kabuki syndrome, KMT2D/MLL2, mosaicism, developmental delay, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Kabuki syndrome (KS) is a rare disorder characterized by multiple congenital anomalies and variable intellectual disability caused by mutations in KMT2D/MLL2 and KDM6A/UTX, two interacting chromatin modifier responsible respectively for 56–75% and 5–8% of the cases. To date, three KS patients with mosaic KMT2D deletions in blood lymphocytes have been described. We report on three additional subjects displaying KMT2D gene mosaics including one in which a single nucleotide change results in a new frameshift mutation (p.L1199HfsX7), and two with already-known nonsense mutations (p.R4484X and p.R5021X). Consistent with previously published cases, mosaic KMT2D mutations may result in mild KS facial dysmorphisms and clinical and neurobehavioral features, suggesting that these characteristics could represent the handles for genetic testing of individuals with slight KS-like traits.

Published
2017
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12. Anti-inflammatory nuclear receptor superfamily in multiple sclerosis patients from Sardinia and Sweden

Author

Xuan Liu, Knut R. Steffensen, Alessandra Sanna, Giannina Arru, Maria Laura Fois, Giulio Rosati, Stefano Sotgiu, Hans Link, Jan-Åke Gustafsson, and Yu-Min Huang

Subjects
Multiple sclerosis, Liver X receptors, Estrogen receptors, Androgen receptor, Sardinia, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Several nuclear hormone receptors have been associated with inflammatory reactions. Particularly, liver X receptors (LXRs) have recently been identified as key transcriptional regulators of genes involved in lipid homeostasis and inflammation. LXRs are negative regulators of macrophage inflammatory gene expression. Multiple sclerosis (MS), a demyelinating disease of the central nervous system of unknown cause, is characterized by recurrent inflammation involving macrophages and their inflammatory mediators. Sweden belongs to the countries with a high MS incidence. In Italy, the MS incidence is lower, except on the island of Sardinia where the incidence is even higher than in Sweden. Subjects from Sardinia are ethnically more homogeneous, and differ from Swedes also regarding genetic background and environment. We studied mRNA expression of several nuclear hormone receptors in blood mononuclear cells (MNC) from female patients with untreated relapsing-remitting MS from Sassari, Sardinia, and Stockholm, Sweden. Sex- and age-matched healthy controls (HC) were from both areas. mRNA expression was evaluated by quantitative real-time PCR. We found altered mRNA expression of LXRs, estrogen receptors (ERs), and androgen receptor (AR) in MS. mRNA expression of both LXRα and LXRβ is lower in MS from Stockholm but not from Sassari. In particular, LXRα mRNA expression was significantly lower in MS from Stockholm as compared with all groups in the study including MS from Sassari. Low levels of ERα mRNA are seen in MS from both Stockholm and Sassari. The splice variant ERβcx showed significantly higher mRNA expression in MS from Sassari and Stockholm as compared with corresponding HC. In particular, ERβcx mRNA in MS from Sassari was remarkably higher as compared with all other groups in the study. Higher levels of AR mRNA are present in HC from Sassari. The findings indicate that the expression levels of anti-inflammatory nuclear receptor superfamily genes in MS appear to reflect both ethnic and environmental influences.

Published
2005
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13. Genes, environment, and susceptibility to multiple sclerosis

Author

Stefano Sotgiu, Maura Pugliatti, Maria Laura Fois, Giannina Arru, Alessandra Sanna, Maria Alessandra Sotgiu, and Giulio Rosati

Subjects
Multiple sclerosis, Epidemiology, Genetics, Virus, Environment, Aetiology, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Multiple sclerosis (MS) is a chronic disease of the central nervous system affecting young adults and thus representing a major burden also for their families and communities. The etiology of MS is obscure and its pathogenesis is yet incompletely depicted. Increased evidences indicate a strong genetic contribution to MS susceptibility, although others support the view that it is also influenced by environmental factors, possibly related to still unidentified pathogens. MS appears to be more heterogeneous than previously believed at the immunological level, and new pathological studies indicate a series of subset of conditions under the common denominator MS. The use of genetically homogeneous and geographically isolated populations at high MS risk, such as that of Sardinia, insular Italy, becomes in principle a vital requirement to reduce biological variables and the intrinsic complexity of the disease.This review will focus on recent findings on the peculiarity of Sardinian MS concerning epidemiological, genetic, and environmental aspects. Epidemiological studies reveal a clear heterogeneous distribution of MS cases in the Northern province of Sassari which may not be uniquely assigned to genetic variations. Furthermore, a different immunogenetic profile, including the association with other immunomediated diseases, and a progressive change in clinical phenotype, including age at onset, are present in this island which gives us unexpected variations at the level of patients' cohort and territorial distribution, especially when the northern province is compared to the southern one. This renders MS etiopathogenesis more complex than formerly thought even in this selected and genetically stable population.

Published
2004
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14. MxA mRNA quantification and disability progression in interferon beta-treated multiple sclerosis patients.

Author

Federico Serana, Luisa Imberti, Maria Pia Amato, Giancarlo Comi, Claudio Gasperini, Angelo Ghezzi, Vittorio Martinelli, Leandro Provinciali, Maria Rosa Rottoli, Stefano Sotgiu, Sergio Stecchi, Michele Vecchio, Mauro Zaffaroni, Cinzia Cordioli, and Ruggero Capra

Subjects
Medicine, Science
Abstract

Even though anti-interferon beta (IFNβ) antibodies are the main determinants of IFNβ bioactivity loss and Myxovirus-resistance protein A (MxA) is the most established marker of IFNβ biological activity in IFNβ-treated multiple sclerosis patients, their usefulness in the routine clinical practice is still debated. Therefore, 118 multiple sclerosis patients naïve for treatment were enrolled for a 3-year longitudinal observational study mimicking the conditions of a real-world setting. In order to evaluate the kinetics of bioactivity loss in blood samples obtained every 6 months after therapy initiation, MxA and interferon receptor isoform/subunit mRNA were quantified by real-time PCR, anti-IFNβ binding antibodies were detected by radioimmunoprecipitation, and neutralizing antibodies by cytopathic effect inhibition assay. Clinical measures of disease activity and disability progression were also obtained at all time points. We found that, at the individual-patient level, the response to IFNβ therapy was extremely heterogeneous, including patients with stable or transitory, early or late loss of IFNβ bioactivity, and patients with samples lacking MxA mRNA induction in spite of absence of antibodies. No interferon receptor isoform alterations that could explain these findings were found. At the group level, none of these biological features correlated with the measures of clinical disease activity or progression. However, when MxA mRNA was evaluated not at the single time point as a dichotomic marker (induced vs. non-induced), but as the mean of its values measured over the 6-to-24 month period, the increasing average MxA predicted a decreasing risk of short-term disability progression, independently from the presence of relapses. Therefore, a more bioactive treatment, even if unable to suppress relapses, reduces their severity by an amount that is proportional to MxA levels. Together with its feasibility in the routine laboratory setting, these data warrant the quantification of MxA mRNA as a primary tool for a routine monitoring of IFNβ therapy.

Published
2014
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15. Expression and activation by Epstein Barr virus of human endogenous retroviruses-W in blood cells and astrocytes: inference for multiple sclerosis.

Author

Giuseppe Mameli, Luciana Poddighe, Alessandra Mei, Elena Uleri, Stefano Sotgiu, Caterina Serra, Roberto Manetti, and Antonina Dolei

Subjects
Medicine, Science
Abstract

BackgroundProposed co-factors triggering the pathogenesis of multiple sclerosis (MS) are the Epstein Barr virus (EBV), and the potentially neuropathogenic MSRV (MS-associated retrovirus) and syncytin-1, of the W family of human endogenous retroviruses.Methodology/principal findingsIn search of links, the expression of HERV-W/MSRV/syncytin-1, with/without exposure to EBV or to EBV glycoprotein350 (EBVgp350), was studied on peripheral blood mononuclear cells (PBMC) from healthy volunteers and MS patients, and on astrocytes, by discriminatory env-specific RT-PCR assays, and by flow cytometry. Basal expression of HERV-W/MSRV/syncytin-1 occurs in astrocytes and in monocytes, NK, and B, but not in T cells. This uneven expression is amplified in untreated MS patients, and dramatically reduced during therapy. In astrocytes, EBVgp350 stimulates the expression of HERV-W/MSRV/syncytin-1, with requirement of the NF-κB pathway. In EBVgp350-treated PBMC, MSRVenv and syncytin-1 transcription is activated in B cells and monocytes, but not in T cells, nor in the highly expressing NK cells. The latter cells, but not the T cells, are activated by proinflammatory cytokines.Conclusions/significanceIn vitro EBV activates the potentially immunopathogenic and neuropathogenic HERV-W/MSRV/syncytin-1, in cells deriving from blood and brain. In vivo, pathogenic outcomes would depend on abnormal situations, as in late EBV primary infection, that is often symptomatic, or/and in the presence of particular host genetic backgrounds. In the blood, HERV-Wenv activation might induce immunopathogenic phenomena linked to its superantigenic properties. In the brain, toxic mechanisms against oligodendrocytes could be established, inducing inflammation, demyelination and axonal damage. Local stimulation by proinflammatory cytokines and other factors might activate further HERV-Ws, contributing to the neuropathogenity. In MS pathogenesis, a possible model could include EBV as initial trigger of future MS, years later, and HERV-W/MSRV/syncytin-1 as actual contributor to MS pathogenicity, in striking parallelism with disease behaviour.

Published
2012
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16. Protein-protein interaction analysis highlights additional loci of interest for multiple sclerosis.

Author

Giammario Ragnedda, Giulio Disanto, Gavin Giovannoni, George C Ebers, Stefano Sotgiu, and Sreeram V Ramagopalan

Subjects
Medicine, Science
Abstract

Genetic factors play an important role in determining the risk of multiple sclerosis (MS). The strongest genetic association in MS is located within the major histocompatibility complex class II region (MHC), but more than 50 MS loci of modest effect located outside the MHC have now been identified. However, the relative candidate genes that underlie these associations and their functions are largely unknown. We conducted a protein-protein interaction (PPI) analysis of gene products coded in loci recently reported to be MS associated at the genome-wide significance level and in loci suggestive of MS association. Our aim was to identify which suggestive regions are more likely to be truly associated, which genes are mostly implicated in the PPI network and their expression profile. From three recent independent association studies, SNPs were considered and divided into significant and suggestive depending on the strength of the statistical association. Using the Disease Association Protein-Protein Link Evaluator tool we found that direct interactions among genetic products were significantly higher than expected by chance when considering both significant regions alone (p

Published
2012
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17. The impact of PM2.5, PM10 and NO2 on Covid-19 severity in a sample of patients with multiple sclerosis: A case-control study

Author

Gianmarco, Abbadessa, Umberto, Aguglia, Lia, Allegorico, Maria, Allegri Rossi Beatrice, Anastasia, Alteno, Pia, Amato Maria, Pietro, Annovazzi, Carlo, Antozzi, Lucia, Appendino, Sebastiano, Arena, Viola, Baione, Roberto, Balgera, Valeria, Barcella, Damiano, Baroncini, Caterina, Barrilà, Mario A, Battaglia, Alessandra, Bellacosa, Gianmarco, Bellucci, Roberto, Bergamaschi, Valeria, Bergamaschi, Daiana, Bezzini, Beatrice, Biolzi, Alvino, Bisecco, Simona, Bonavita, Giovanna, Borriello, Chiara, Bosa, Antonio, Bosco, Francesca, Bovis, Marco, Bozzali, Laura, Brambilla, Vincenzo, Brescia Morra, Giampaolo, Brichetto, Maria, Buccafusca, Elisabetta, Bucciantini, Sebastiano, Bucello, Chiara, Buscarinu Maria, Paola, Cabboi Maria, Massimiliano, Calabrese, Francesca, Calabria, Francesca, Caleri, Federico, Camilli, Maria, Caniatti Luisa, Roberto, Cantello, Marco, Capobianco, Ruggero, Capra, Rocco, Capuano, Luca, Carmisciano, Patrizia, Carta, Paola, Cavalla, Grazia, Celani Maria, Maria, Cellerino, Raffaella, Cerqua, Clara, Chisari, Raffaella, Clerici, Marinella, Clerico, Eleonora, Cocco, Gaia, Cola, Giancarlo, Comi, Paolo, Confalonieri, Antonella, Conte, Zaffira, Conti Marta, Christian, Cordano, Susanna, Cordera, Cinzia, Cordioli, Francesco, Corea, Claudio, Correale, Salvatore, Cottone, Francesco, Crescenzo, Erica, Curti, Alessandro, d'Ambrosio, Emanuele, D'Amico, Chiara, Danni Maura, Alessia, d'Arma, Vincenzo, Dattola, Stefano, de Biase, Giovanna, De Luca, Federica, De Mercanti Stefania, Paolo, De Mitri, Nicola, De Rossi, Nicola, De Stefano, Maria, Della Cava Fabio, Marco, Della Cava, Sonia, Di Lemme, Mario, di Napoli, Alessia, Di Sapio, Renato, Docimo, Anna, Dutto, Luana, Evangelista, Salvatore, Fanara, Roberta, Fantozzi, Diana, Ferraro, Teresa, Ferrò Maria, Massimo, Filippi, Cristina, Fioretti, Mario, Fratta, Jessica, Frau, Marzia, Fronza, Roberto, Furlan, Alberto, Gajofatto, Antonio, Gallo, Paolo, Gallo, Claudio, Gasperini, Anna, Ghazaryan, Bruno, Giometto, Francesca, Gobbin, Flora, Govone, Franco, Granella, Erica, Grange, Grazia, Grasso Maria, Luigi ME, Grimaldi, Angelica, Guareschi, Clara, Guaschino, Simone, Guerrieri, Donata, Guidetti, Barbara, Juergenson Ina, Pietro, Iaffaldano, Antonio, Ianniello, Luigi, Iasevoli, Paolo, Immovilli, Daniele, Imperiale, Teresa, Infante Maria, Matilde, Inglese, Rosa, Iodice, Aniello, Iovino, Giovanna, Konrad, Doriana, Landi, Roberta, Lanzillo, Caterina, Lapucci, Luigi, Lavorgna, Rita, L'Episcopo Maria, Serena, Leva, Giuseppe, Liberatore, Marianna, Lo Re, Marco, Longoni, Leonardo, Lopiano, Lorena, Lorefice, Matteo, Lucchini, Giacomo, Lus, Davide, Maimone, Maria, Malentacchi, Giulia, Mallucci, Simona, Malucchi, Rosa, Mancinelli Chiara, Luca, Mancinelli, Paolo, Manganotti, Teresa, Maniscalco Giorgia, Vittorio, Mantero, Sabrina, Marangoni, Damiano, Marastoni, Alessandra, Marfia Girolama, Fabiana, Marinelli, Alessandro, Marti, Filippo, Martinelli Boneschi, Federco, Masserano Zoli, Francesca, Matta, Laura, Mendozzi, Giuseppe, Meucci, Silvia, Miante, Giuseppina, Miele, Eva, Milano, Massimiliano, Mirabella, Rosanna, Missione, Marcello, Moccia, Lucia, Moiola, Sara, Montepietra, Margherita, MontiBragadin, Federico, Montini, Roberta, Motta, Raffaele, Nardone, Gabri, Nicoletti Carolina, Eduardo, Nobile-Orazio, Agostino, Nozzolillo, Marco, Onofrj, Riccardo, Orlandi, Anna, Palmieri, Damiano, Paolicelli, Livia, Pasquali, Fulvio, Pasquin, Luisa, Pastò, Francesco, Patti, Elisabetta, Pedrazzoli, Paola, Perini, Ilaria, Pesci, Maria, Petracca, Alfredo, Petrone, Carlo, Piantadosi, Anna M, Pietroboni, Federica, Pinardi, Marta, Ponzano, Emilio, Portaccio, Mattia, Pozzato, Carlo, Pozzilli, Luca, Prosperini, Alessandra, Protti, Eugenio, Pucci, Marta, Radaelli, Paolo, Ragonese, Sarah, Rasia, Sabrina, Realmuto, Anna, Repice, Eleonora, Rigoni, Teresa, Rilla Maria, Francesca, Rinaldi, Marcello, Romano Calogero, Marco, Ronzoni, Marco, Rovaris, Francesca, Ruscica, Loredana, Sabattini, Giuseppe, Salemi, Marco, Salvetti, Lorenzo, Saraceno, Alessia, Sartori, Arianna, Sartori, Elvira, Sbragia, Cinzia, Scandellari, Ilaria, Scarano Giuditta, Valentina, Scarano, Irene, Schiavetti, Maria, Sessa, Caterina, Sgarito, Grazia, Sibilia, Gabriele, Siciliano, Alessio, Signori, Elisabetta, Signoriello, Leonardo, Sinisi, Francesca, Sireci, Patrizia, Sola, Claudio, Solaro, Pia, Sormani Maria, Stefano, Sotgiu, Maddalena, Sparaco, Laura, Stromillo Maria, Silvia, Strumia, Laura, Susani Emanuela, Giulietta, Tabiadon, Francesco, Teatini, Gioacchino, Tedeschi, Valentina, Tomassini, Simone, Tonietti, Valentina, Torri Clerici, Carla, Tortorella, Simona, Toscano, Rocco, Totaro, Maria, Trojano, Maria, Trotta, Gabriella, Turano, Monica, Ulivelli, Manzo, Valentino, Giovanna, Vaula, Domizia, Vecchio, Marco, Vercellino, Pinuccia, Verrengia Elena, Marika, Vianello, Eleonora, Virgilio, Francesca, Vitetta, Stefano, Vollaro, Mauro, Zaffaroni, Mauro, Zampolini, Roberto, Zarbo Ignazio, Antonio, Zito, Luigi, Zuliani, Ponzano, Marta, Schiavetti, Irene, Bergamaschi, Roberto, Pisoni, Enrico, Bellavia, Andrea, Mallucci, Giulia, Carmisciano, Luca, Inglese, Matilde, Cordioli, Cinzia, Marfia, Girolama Alessandra, Cocco, Eleonora, Immovilli, Paolo, Pesci, Ilaria, Scandellari, Cinzia, Cavalla, Paola, Radaelli, Marta, Vianello, Marika, Vitetta, Francesca, Montepietra, Sara, Amato, Maria Pia, Fioretti, Cristina, Filippi, Massimo, Sartori, Arianna, Caleri, Francesca, Clerico, Marinella, Gallo, Antonio, Conte, Antonella, Clerici, Raffaella, De Luca, Giovanna, Boneschi, Filippo Martinelli, Cantello, Roberto, Calabrese, Massimiliano, Tortorella, Carla, Rovaris, Marco, Verrengia, Elena Pinuccia, Patti, Francesco, Morra, Vincenzo Brescia, Salvetti, Marco, and Sormani, Maria Pia

Published
2022
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19. Le disposizioni sui Comuni per il 2022: una rassegna normativa in un quadro di incertezza

Author

Massimo Allulli, Romano Astolfo, Gioacchino Benfante, Chiara Bergonzini, Paolo Biancone, Manuela Braione, Paolo Brambilla, Valerio Brescia, Vinicio Brigante, Noemi Ilaria Buonsante, Federico Caldura, Stefano Campostrini, Federico Chmet, Filippo D’Angelo, Simone D’Antonio, Marcello Degni, Elena Di Carpegna Brivio, Marco Di Cataldo, Antonio Di Stasio, Veronica Dini, Leonardo Draghetti, Simona Elmo, Elena Faccin, Fabrizio Fazioli, Giancarlo Ferrara, Andrea Ferri, Antonio Floridia, Giaime Gabrielli, Alessandro Giordano, Chiara Grasso, Rodolfo Lewanski, Eleonora Luciani, Vanessa Manzetti, Edoardo Meneghelli, Paolo Mezzanotte, Francesco Monaco, Andrea Morgia, Samuele Nannoni, Maria Teresa Nardo, Simone Ombuen, Carolina Pacchi, Alessandra Poggiani, Foscara Porchia, Stefania Porchia, Paola Pucci, Giuliano Resce, Giulia Romani, Luciano Sandel, Silvana Secinaro, Giulia Sonzogno, Stefano Sotgiu, Claudia Tubertini, Matteo Turrin, Maristella Zantedeschi., Degni, M, Luciani, E, Fabrizio, F, Luciani, E., Fabrizio, F., Massimo Allulli, Romano Astolfo, Gioacchino Benfante, Chiara Bergonzini, Paolo Biancone, Manuela Braione, Paolo Brambilla, Valerio Brescia, Vinicio Brigante, Noemi Ilaria Buonsante, Federico Caldura, Stefano Campostrini, Federico Chmet, Filippo D’Angelo, Simone D’Antonio, Marcello Degni, Elena Di Carpegna Brivio, Marco Di Cataldo, Antonio Di Stasio, Veronica Dini, Leonardo Draghetti, Simona Elmo, Elena Faccin, Fabrizio Fazioli, Giancarlo Ferrara, Andrea Ferri, Antonio Floridia, Giaime Gabrielli, Alessandro Giordano, Chiara Grasso, Rodolfo Lewanski, Eleonora Luciani, Vanessa Manzetti, Edoardo Meneghelli, Paolo Mezzanotte, Francesco Monaco, Andrea Morgia, Samuele Nannoni, Maria Teresa Nardo, Simone Ombuen, Carolina Pacchi, Alessandra Poggiani, Foscara Porchia, Stefania Porchia, Paola Pucci, Giuliano Resce, Giulia Romani, Luciano Sandel, Silvana Secinaro, Giulia Sonzogno, Stefano Sotgiu, Claudia Tubertini, Matteo Turrin, Maristella Zantedeschi., Degni, M, Luciani, E, Fabrizio, F, Luciani, E., and Fabrizio, F.

Published
2023

20. The effect of air pollution on COVID‐19 severity in a sample of patients with multiple sclerosis

Author

Bergamaschi, Roberto, Ponzano, Marta, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Filippi, Massimo, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, De Rossi, Nicola, Brichetto, Giampaolo, Cocco, Eleonora, Scandellari, Cinzia, Cavalla, Paola, Pesci, Ilaria, Zito, Antonio, Confalonieri, Paolo, Marfia, Girolama Alessandra, Perini, Paola, Inglese, Matilde, Trojano, Maria, Brescia Morra, Vincenzo, Pisoni, Enrico, Tedeschi, Gioacchino, Comi, Giancarlo, Battaglia, Mario Alberto, Patti, Francesco, Salvetti, Marco, Sormani, Maria Pia, Gianmarco Abbadessa, Umberto Aguglia, Lia Allegorico, Rossi Beatrice Maria Allegri, Anastasia Alteno, Maria Pia Amato, Pietro Annovazzi, Carlo Antozzi, Lucia Appendino, Sebastiano Arena, Viola Baione, Roberto Balgera, Valeria Barcella, Damiano Baroncini, Caterina Barrilà, Mario A Battaglia, Alessandra Bellacosa, Gianmarco Bellucci, Roberto Bergamaschi, Valeria Bergamaschi, Daiana Bezzini, Beatrice Biolzi, Alvino Bisecco, Simona Bonavita, Giovanna Borriello, Chiara Bosa, Antonio Bosco, Francesca Bovis, Marco Bozzali, Laura Brambilla, Morra Vincenzo Brescia, Giampaolo Brichetto, Maria Buccafusca, Elisabetta Bucciantini, Sebastiano Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano Calabrese, Francesca Calabria, Francesca Caleri, Federico Camilli, Luisa Maria Caniatti, Roberto Cantello, Marco Capobianco, Ruggero Capra, Rocco Capuano, Luca Carmisciano, Patrizia Carta, Paola Cavalla, Maria Grazia Celani, Maria Cellerino, Raffaella Cerqua, Clara Chisari, Raffaella Clerici, Marinella Clerico, Eleonora Cocco, Gaia Cola, Giancarlo Comi, Paolo Confalonieri, Antonella Conte, Marta Zaffira Conti, Christian Cordano, Susanna Cordera, Cinzia Cordioli, Francesco Corea, Claudio Correale, Salvatore Cottone, Francesco Crescenzo, Erica Curti, Alessandro d'Ambrosio, Emanuele D'Amico, Maura Chiara Danni, Alessia d'Arma, Vincenzo Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Rossi, Nicola De Stefano, Cava Marco Della, Mario di Napoli, Alessia Di Sapio, Renato Docimo, Anna Dutto, Luana Evangelista, Salvatore Fanara, Diana Ferraro, Maria Teresa Ferrò, Massimo Filippi, Cristina Fioretti, Mario Fratta, Jessica Frau, Marzia Fronza, Roberto Furlan, Alberto Gajofatto, Antonio Gallo, Paolo Gallo, Claudio Gasperini, Anna Ghazaryan, Bruno Giometto, Francesca Gobbin, Flora Govone, Franco Granella, Erica Grange, Maria Grazia Grasso, Angelica Guareschi, Clara Guaschino, Simone Guerrieri, Donata Guidetti, Pietro Iaffaldano, Antonio Ianniello, Luigi Iasevoli, Paolo Immovilli, Daniele Imperiale, Maria Teresa Infante, Matilde Inglese, Rosa Iodice, Aniello Iovino, Giovanna Konrad, Doriana Landi, Roberta Lanzillo, Caterina Lapucci, Luigi Lavorgna, Maria Rita L'Episcopo, Serena Leva, Giuseppe Liberatore, Re Marianna Lo, Marco Longoni, Leonardo Lopiano, Lorena Lorefice, Matteo Lucchini, Giacomo Lus, Davide Maimone, Maria Malentacchi, Giulia Mallucci, Simona Malucchi, Chiara Rosa Mancinelli, Luca Mancinelli, Paolo Manganotti, Giorgia Teresa Maniscalco, Vittorio Mantero, Sabrina Marangoni, Damiano Marastoni, Girolama Alessandra Marfia, Fabiana Marinelli, Alessandro Marti, Boneschi Filippo Martinelli, Zoli Federco Masserano, Francesca Matta, Laura Mendozzi, Giuseppe Meucci, Silvia Miante, Giuseppina Miele, Eva Milano, Massimiliano Mirabella, Rosanna Missione, Marcello Moccia, Lucia Moiola, Sara Montepietra, Margherita MontiBragadin, Federico Montini, Roberta Motta, Raffaele Nardone, Carolina Gabri Nicoletti, Eduardo Nobile-Orazio, Agostino Nozzolillo, Marco Onofrj, Riccardo Orlandi, Anna Palmieri, Damiano Paolicelli, Livia Pasquali, Luisa Pastò, Francesco Patti, Elisabetta Pedrazzoli, Paola Perini, Ilaria Pesci, Maria Petracca, Alfredo Petrone, Carlo Piantadosi, Anna M Pietroboni, Federica Pinardi, Marta Ponzano, Emilio Portaccio, Mattia Pozzato, Carlo Pozzilli, Luca Prosperini, Alessandra Protti, Marta Radaelli, Paolo Ragonese, Sarah Rasia, Sabrina Realmuto, Anna Repice, Eleonora Rigoni, Maria Teresa Rilla, Francesca Rinaldi, Calogero Marcello Romano, Marco Ronzoni, Marco Rovaris, Francesca Ruscica, Loredana Sabattini, Giuseppe Salemi, Marco Salvetti, Lorenzo Saraceno, Alessia Sartori, Arianna Sartori, Elvira Sbragia, Cinzia Scandellari, Giuditta Ilaria Scarano, Valentina Scarano, Irene Schiavetti, Maria Sessa, Caterina Sgarito, Grazia Sibilia, Gabriele Siciliano, Alessio Signori, Elisabetta Signoriello, Leonardo Sinisi, Francesca Sireci, Patrizia Sola, Claudio Solaro, Maria Pia Sormani, Stefano Sotgiu, Maddalena Sparaco, Maria Laura Stromillo, Silvia Strumia, Emanuela Laura Susani, Giulietta Tabiadon, Francesco Teatini, Gioacchino Tedeschi, Valentina Tomassini, Simone Tonietti, Clerici Valentina Torri, Carla Tortorella, Simona Toscano, Rocco Totaro, Maria Trojano, Maria Trotta, Gabriella Turano, Monica Ulivelli, Manzo Valentino, Giovanna Vaula, Domizia Vecchio, Marco Vercellino, Elena Pinuccia Verrengia, Marika Vianello, Eleonora Virgilio, Francesca Vitetta, Stefano Vollaro, Mauro Zaffaroni, Mauro Zampolini, Ignazio Roberto Zarbo, Antonio Zito, Luigi Zuliani, Bergamaschi, R, Ponzano, M, Schiavetti, I, Carmisciano, L, Cordioli, C, Filippi, M, Radaelli, M, Immovilli, P, Capobianco, M, De Rossi, N, Brichetto, G, Cocco, E, Scandellari, C, Cavalla, P, Pesci, I, Zito, A, Confalonieri, P, Marfia, Ga, Perini, P, Inglese, M, Trojano, M, Brescia Morra, V, Pisoni, E, Tedeschi, G, Comi, G, Battaglia, Ma, Patti, F, Salvetti, M, Sormani, Mp, Abbadessa, Gianmarco, Umberto, Aguglia, Lia, Allegorico, Rossi Beatrice Maria Allegri, Anastasia, Alteno, Maria Pia Amato, Pietro, Annovazzi, Carlo, Antozzi, Lucia, Appendino, Sebastiano, Arena, Viola, Baione, Roberto, Balgera, Valeria, Barcella, Damiano, Baroncini, Caterina, Barrilà, Mario, A Battaglia, Alessandra, Bellacosa, Gianmarco, Bellucci, Roberto, Bergamaschi, Valeria, Bergamaschi, Daiana, Bezzini, Beatrice, Biolzi, Bisecco, Alvino, Bonavita, Simona, Giovanna, Borriello, Chiara, Bosa, Bosco, Antonio, Francesca, Bovi, Marco, Bozzali, Laura, Brambilla, Morra Vincenzo Brescia, Giampaolo, Brichetto, Maria, Buccafusca, Elisabetta, Bucciantini, Sebastiano, Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano, Calabrese, Francesca, Calabria, Francesca, Caleri, Federico, Camilli, Luisa Maria Caniatti, Roberto, Cantello, Marco, Capobianco, Ruggero, Capra, Capuano, Rocco, Luca, Carmisciano, Patrizia, Carta, Paola, Cavalla, Maria Grazia Celani, Maria, Cellerino, Raffaella, Cerqua, Clara, Chisari, Raffaella, Clerici, Marinella, Clerico, Eleonora, Cocco, Gaia, Cola, Giancarlo, Comi, Paolo, Confalonieri, Antonella, Conte, Marta Zaffira Conti, Christian, Cordano, Susanna, Cordera, Cinzia, Cordioli, Corea, Francesco, Claudio, Correale, Salvatore, Cottone, Francesco, Crescenzo, Erica, Curti, Alessandro, D'Ambrosio, Emanuele, D'Amico, Maura Chiara Danni, Alessia, D'Arma, Vincenzo, Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Rossi, Nicola De Stefano, Cava Marco Della, Mario di Napoli, Alessia Di Sapio, Docimo, Renato, Anna, Dutto, Luana, Evangelista, Salvatore, Fanara, Diana, Ferraro, Maria Teresa Ferrò, Massimo, Filippi, Cristina, Fioretti, Fratta, Mario, Jessica, Frau, Marzia, Fronza, Roberto, Furlan, Alberto, Gajofatto, Gallo, Antonio, Paolo, Gallo, Claudio, Gasperini, Anna, Ghazaryan, Bruno, Giometto, Francesca, Gobbin, Flora, Govone, Franco, Granella, Erica, Grange, Maria Grazia Grasso, Angelica, Guareschi, Clara, Guaschino, Simone, Guerrieri, Donata, Guidetti, Pietro, Iaffaldano, Antonio, Ianniello, Luigi, Iasevoli, Paolo, Immovilli, Daniele, Imperiale, Maria Teresa Infante, Matilde, Inglese, Rosa, Iodice, Aniello, Iovino, Giovanna, Konrad, Doriana, Landi, Roberta, Lanzillo, Caterina, Lapucci, Luigi, Lavorgna, Maria Rita L'Episcopo, Serena, Leva, Giuseppe, Liberatore, Re Marianna Lo, Marco, Longoni, Leonardo, Lopiano, Lorena, Lorefice, Matteo, Lucchini, Lus, Giacomo, Davide, Maimone, Maria, Malentacchi, Giulia, Mallucci, Simona, Malucchi, Chiara Rosa Mancinelli, Luca, Mancinelli, Paolo, Manganotti, Giorgia Teresa Maniscalco, Vittorio, Mantero, Sabrina, Marangoni, Damiano, Marastoni, Girolama Alessandra Marfia, Fabiana, Marinelli, Alessandro, Marti, Boneschi Filippo Martinelli, Zoli Federco Masserano, Francesca, Matta, Laura, Mendozzi, Giuseppe, Meucci, Silvia, Miante, Miele, Giuseppina, Eva, Milano, Massimiliano, Mirabella, Missione, Rosanna, Marcello, Moccia, Lucia, Moiola, Sara, Montepietra, Margherita, Montibragadin, Federico, Montini, Roberta, Motta, Raffaele, Nardone, Carolina Gabri Nicoletti, Eduardo, Nobile-Orazio, Agostino, Nozzolillo, Marco, Onofrj, Riccardo, Orlandi, Palmieri, Anna, Damiano, Paolicelli, Livia, Pasquali, Luisa, Pastò, Francesco, Patti, Elisabetta, Pedrazzoli, Paola, Perini, Ilaria, Pesci, Maria, Petracca, Alfredo, Petrone, Carlo, Piantadosi, Anna, M Pietroboni, Federica, Pinardi, Marta, Ponzano, Emilio, Portaccio, Mattia, Pozzato, Carlo, Pozzilli, Luca, Prosperini, Alessandra, Protti, Marta, Radaelli, Paolo, Ragonese, Sarah, Rasia, Sabrina, Realmuto, Anna, Repice, Eleonora, Rigoni, Maria Teresa Rilla, Francesca, Rinaldi, Calogero Marcello Romano, Marco, Ronzoni, Marco, Rovari, Francesca, Ruscica, Loredana, Sabattini, Giuseppe, Salemi, Marco, Salvetti, Lorenzo, Saraceno, Alessia, Sartori, Arianna, Sartori, Elvira, Sbragia, Cinzia, Scandellari, Giuditta Ilaria Scarano, Valentina, Scarano, Irene, Schiavetti, Maria, Sessa, Caterina, Sgarito, Grazia, Sibilia, Gabriele, Siciliano, Alessio, Signori, Signoriello, Elisabetta, Leonardo, Sinisi, Francesca, Sireci, Patrizia, Sola, Claudio, Solaro, Maria Pia Sormani, Stefano, Sotgiu, Sparaco, Maddalena, Maria Laura Stromillo, Silvia, Strumia, Emanuela Laura Susani, Giulietta, Tabiadon, Francesco, Teatini, Tedeschi, Gioacchino, Valentina, Tomassini, Simone, Tonietti, Clerici Valentina Torri, Carla, Tortorella, Simona, Toscano, Rocco, Totaro, Maria, Trojano, Trotta, Maria Consiglia, Gabriella, Turano, Monica, Ulivelli, Manzo, Valentino, Giovanna, Vaula, Domizia, Vecchio, Marco, Vercellino, Elena Pinuccia Verrengia, Marika, Vianello, Eleonora, Virgilio, Francesca, Vitetta, Stefano, Vollaro, Mauro, Zaffaroni, Mauro, Zampolini, Ignazio Roberto Zarbo, Zito, Guido Antonio, Bergamaschi, R., Ponzano, M., Schiavetti, I., Carmisciano, L., Cordioli, C., Filippi, M., Radaelli, M., Immovilli, P., Capobianco, M., De Rossi, N., Brichetto, G., Cocco, E., Scandellari, C., Cavalla, P., Pesci, I., Zito, A., Confalonieri, P., Marfia, G. A., Perini, P., Inglese, M., Trojano, M., Brescia Morra, V., Pisoni, E., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., Sormani, M. P., Bergamaschi, Roberto, Ponzano, Marta, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Filippi, Massimo, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, De Rossi, Nicola, Brichetto, Giampaolo, Cocco, Eleonora, Scandellari, Cinzia, Cavalla, Paola, Pesci, Ilaria, Zito, Antonio, Confalonieri, Paolo, Marfia, Girolama Alessandra, Perini, Paola, Inglese, Matilde, Trojano, Maria, Brescia Morra, Vincenzo, Pisoni, Enrico, Comi, Giancarlo, Battaglia, Mario Alberto, Patti, Francesco, Salvetti, Marco, Sormani, Maria, Pia, Gianmarco, Abbadessa, Alvino, Bisecco, Simona, Bonavita, Antonio, Bosco, Rocco, Capuano, Francesco, Corea, Renato, Docimo, Mario, Fratta, Antonio, Gallo, Iodice, Rosa, Iovino, Aniello, Lanzillo, Roberta, Giacomo, Lu, Giuseppina, Miele, Rosanna, Missione, Moccia, Marcello, Anna, Palmieri, Elisabetta, Signoriello, Maddalena, Sparaco, Gioacchino, Tedeschi, Maria, Trotta, Antonio, Zito, and Luigi, Zuliani

Subjects
air pollution, coronavirus, multiple sclerosis, medicine.medical_specialty, Multivariate analysis, Coronavirus disease 2019 (COVID-19), Clinical Sciences, Air pollution, Sample (statistics), Neurodegenerative, Settore MED/26, medicine.disease_cause, Autoimmune Disease, law.invention, Sustainable Cities and Communities, Clinical Research, law, Humans, Medicine, Climate-Related Exposures and Conditions, Neurology & Neurosurgery, MuSC-19 study group, SARS-CoV-2, business.industry, Multiple sclerosis, Neurosciences, COVID-19, Retrospective cohort study, Original Articles, medicine.disease, Intensive care unit, Particulate Matter, Air Pollution, Multiple Sclerosis, Brain Disorders, coronaviru, Settore MED/26 - NEUROLOGIA, Good Health and Well Being, Neurology, multiple sclerosi, Emergency medicine, Original Article, Neurology (clinical), Ordered logit, business, Human
Abstract

Background and purpose Some studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m3 (PM2.5), may contribute to severe COVID‐19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID‐19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID‐19 severity amongst PwMS. Methods Data were retrieved from an Italian web‐based platform (MuSC‐19) which includes PwMS with COVID‐19. PM2.5 2016–2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID‐19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID‐19 severity. Results In all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID‐19 course (odds ratio 1.90; p = 0.009). Conclusions Even if several other factors explain the unfavourable course of COVID‐19 in PwMS, the role of air pollutants must be considered and further investigated., Air pollution, often assessed by particulate matter with diameter below 2.5 µg/m3, may contribute to severe COVID‐19 courses. 1087 patients were included, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died. Even if several other factors explain the unfavourable course of COVID‐19 in patients with multiple sclerosis, the role of air pollutants must be considered and further investigated.

Published
2021

23. The impact of PM2.5, PM10 and NO2 on Covid-19 severity in a sample of patients with multiple sclerosis: A case-control study

Author

Ponzano, Marta, primary, Schiavetti, Irene, additional, Bergamaschi, Roberto, additional, Pisoni, Enrico, additional, Bellavia, Andrea, additional, Mallucci, Giulia, additional, Carmisciano, Luca, additional, Inglese, Matilde, additional, Cordioli, Cinzia, additional, Marfia, Girolama Alessandra, additional, Cocco, Eleonora, additional, Immovilli, Paolo, additional, Pesci, Ilaria, additional, Scandellari, Cinzia, additional, Cavalla, Paola, additional, Radaelli, Marta, additional, Vianello, Marika, additional, Vitetta, Francesca, additional, Montepietra, Sara, additional, Amato, Maria Pia, additional, Fioretti, Cristina, additional, Filippi, Massimo, additional, Sartori, Arianna, additional, Caleri, Francesca, additional, Clerico, Marinella, additional, Gallo, Antonio, additional, Conte, Antonella, additional, Clerici, Raffaella, additional, De Luca, Giovanna, additional, Boneschi, Filippo Martinelli, additional, Cantello, Roberto, additional, Calabrese, Massimiliano, additional, Tortorella, Carla, additional, Rovaris, Marco, additional, Verrengia, Elena Pinuccia, additional, Patti, Francesco, additional, Morra, Vincenzo Brescia, additional, Salvetti, Marco, additional, Sormani, Maria Pia, additional, Gianmarco, Abbadessa, additional, Umberto, Aguglia, additional, Lia, Allegorico, additional, Maria, Allegri Rossi Beatrice, additional, Anastasia, Alteno, additional, Pia, Amato Maria, additional, Pietro, Annovazzi, additional, Carlo, Antozzi, additional, Lucia, Appendino, additional, Sebastiano, Arena, additional, Viola, Baione, additional, Roberto, Balgera, additional, Valeria, Barcella, additional, Damiano, Baroncini, additional, Caterina, Barrilà, additional, Mario A, Battaglia, additional, Alessandra, Bellacosa, additional, Gianmarco, Bellucci, additional, Roberto, Bergamaschi, additional, Valeria, Bergamaschi, additional, Daiana, Bezzini, additional, Beatrice, Biolzi, additional, Alvino, Bisecco, additional, Simona, Bonavita, additional, Giovanna, Borriello, additional, Chiara, Bosa, additional, Antonio, Bosco, additional, Francesca, Bovis, additional, Marco, Bozzali, additional, Laura, Brambilla, additional, Vincenzo, Brescia Morra, additional, Giampaolo, Brichetto, additional, Maria, Buccafusca, additional, Elisabetta, Bucciantini, additional, Sebastiano, Bucello, additional, Chiara, Buscarinu Maria, additional, Paola, Cabboi Maria, additional, Massimiliano, Calabrese, additional, Francesca, Calabria, additional, Francesca, Caleri, additional, Federico, Camilli, additional, Maria, Caniatti Luisa, additional, Roberto, Cantello, additional, Marco, Capobianco, additional, Ruggero, Capra, additional, Rocco, Capuano, additional, Luca, Carmisciano, additional, Patrizia, Carta, additional, Paola, Cavalla, additional, Grazia, Celani Maria, additional, Maria, Cellerino, additional, Raffaella, Cerqua, additional, Clara, Chisari, additional, Raffaella, Clerici, additional, Marinella, Clerico, additional, Eleonora, Cocco, additional, Gaia, Cola, additional, Giancarlo, Comi, additional, Paolo, Confalonieri, additional, Antonella, Conte, additional, Zaffira, Conti Marta, additional, Christian, Cordano, additional, Susanna, Cordera, additional, Cinzia, Cordioli, additional, Francesco, Corea, additional, Claudio, Correale, additional, Salvatore, Cottone, additional, Francesco, Crescenzo, additional, Erica, Curti, additional, Alessandro, d'Ambrosio, additional, Emanuele, D'Amico, additional, Chiara, Danni Maura, additional, Alessia, d'Arma, additional, Vincenzo, Dattola, additional, Stefano, de Biase, additional, Giovanna, De Luca, additional, Federica, De Mercanti Stefania, additional, Paolo, De Mitri, additional, Nicola, De Rossi, additional, Nicola, De Stefano, additional, Maria, Della Cava Fabio, additional, Marco, Della Cava, additional, Sonia, Di Lemme, additional, Mario, di Napoli, additional, Alessia, Di Sapio, additional, Renato, Docimo, additional, Anna, Dutto, additional, Luana, Evangelista, additional, Salvatore, Fanara, additional, Roberta, Fantozzi, additional, Diana, Ferraro, additional, Teresa, Ferrò Maria, additional, Massimo, Filippi, additional, Cristina, Fioretti, additional, Mario, Fratta, additional, Jessica, Frau, additional, Marzia, Fronza, additional, Roberto, Furlan, additional, Alberto, Gajofatto, additional, Antonio, Gallo, additional, Paolo, Gallo, additional, Claudio, Gasperini, additional, Anna, Ghazaryan, additional, Bruno, Giometto, additional, Francesca, Gobbin, additional, Flora, Govone, additional, Franco, Granella, additional, Erica, Grange, additional, Grazia, Grasso Maria, additional, Luigi ME, Grimaldi, additional, Angelica, Guareschi, additional, Clara, Guaschino, additional, Simone, Guerrieri, additional, Donata, Guidetti, additional, Barbara, Juergenson Ina, additional, Pietro, Iaffaldano, additional, Antonio, Ianniello, additional, Luigi, Iasevoli, additional, Paolo, Immovilli, additional, Daniele, Imperiale, additional, Teresa, Infante Maria, additional, Matilde, Inglese, additional, Rosa, Iodice, additional, Aniello, Iovino, additional, Giovanna, Konrad, additional, Doriana, Landi, additional, Roberta, Lanzillo, additional, Caterina, Lapucci, additional, Luigi, Lavorgna, additional, Rita, L'Episcopo Maria, additional, Serena, Leva, additional, Giuseppe, Liberatore, additional, Marianna, Lo Re, additional, Marco, Longoni, additional, Leonardo, Lopiano, additional, Lorena, Lorefice, additional, Matteo, Lucchini, additional, Giacomo, Lus, additional, Davide, Maimone, additional, Maria, Malentacchi, additional, Giulia, Mallucci, additional, Simona, Malucchi, additional, Rosa, Mancinelli Chiara, additional, Luca, Mancinelli, additional, Paolo, Manganotti, additional, Teresa, Maniscalco Giorgia, additional, Vittorio, Mantero, additional, Sabrina, Marangoni, additional, Damiano, Marastoni, additional, Alessandra, Marfia Girolama, additional, Fabiana, Marinelli, additional, Alessandro, Marti, additional, Filippo, Martinelli Boneschi, additional, Federco, Masserano Zoli, additional, Francesca, Matta, additional, Laura, Mendozzi, additional, Giuseppe, Meucci, additional, Silvia, Miante, additional, Giuseppina, Miele, additional, Eva, Milano, additional, Massimiliano, Mirabella, additional, Rosanna, Missione, additional, Marcello, Moccia, additional, Lucia, Moiola, additional, Sara, Montepietra, additional, Margherita, MontiBragadin, additional, Federico, Montini, additional, Roberta, Motta, additional, Raffaele, Nardone, additional, Gabri, Nicoletti Carolina, additional, Eduardo, Nobile-Orazio, additional, Agostino, Nozzolillo, additional, Marco, Onofrj, additional, Riccardo, Orlandi, additional, Anna, Palmieri, additional, Damiano, Paolicelli, additional, Livia, Pasquali, additional, Fulvio, Pasquin, additional, Luisa, Pastò, additional, Francesco, Patti, additional, Elisabetta, Pedrazzoli, additional, Paola, Perini, additional, Ilaria, Pesci, additional, Maria, Petracca, additional, Alfredo, Petrone, additional, Carlo, Piantadosi, additional, Anna M, Pietroboni, additional, Federica, Pinardi, additional, Marta, Ponzano, additional, Emilio, Portaccio, additional, Mattia, Pozzato, additional, Carlo, Pozzilli, additional, Luca, Prosperini, additional, Alessandra, Protti, additional, Eugenio, Pucci, additional, Marta, Radaelli, additional, Paolo, Ragonese, additional, Sarah, Rasia, additional, Sabrina, Realmuto, additional, Anna, Repice, additional, Eleonora, Rigoni, additional, Teresa, Rilla Maria, additional, Francesca, Rinaldi, additional, Marcello, Romano Calogero, additional, Marco, Ronzoni, additional, Marco, Rovaris, additional, Francesca, Ruscica, additional, Loredana, Sabattini, additional, Giuseppe, Salemi, additional, Marco, Salvetti, additional, Lorenzo, Saraceno, additional, Alessia, Sartori, additional, Arianna, Sartori, additional, Elvira, Sbragia, additional, Cinzia, Scandellari, additional, Ilaria, Scarano Giuditta, additional, Valentina, Scarano, additional, Irene, Schiavetti, additional, Maria, Sessa, additional, Caterina, Sgarito, additional, Grazia, Sibilia, additional, Gabriele, Siciliano, additional, Alessio, Signori, additional, Elisabetta, Signoriello, additional, Leonardo, Sinisi, additional, Francesca, Sireci, additional, Patrizia, Sola, additional, Claudio, Solaro, additional, Pia, Sormani Maria, additional, Stefano, Sotgiu, additional, Maddalena, Sparaco, additional, Laura, Stromillo Maria, additional, Silvia, Strumia, additional, Laura, Susani Emanuela, additional, Giulietta, Tabiadon, additional, Francesco, Teatini, additional, Gioacchino, Tedeschi, additional, Valentina, Tomassini, additional, Simone, Tonietti, additional, Valentina, Torri Clerici, additional, Carla, Tortorella, additional, Simona, Toscano, additional, Rocco, Totaro, additional, Maria, Trojano, additional, Maria, Trotta, additional, Gabriella, Turano, additional, Monica, Ulivelli, additional, Manzo, Valentino, additional, Giovanna, Vaula, additional, Domizia, Vecchio, additional, Marco, Vercellino, additional, Pinuccia, Verrengia Elena, additional, Marika, Vianello, additional, Eleonora, Virgilio, additional, Francesca, Vitetta, additional, Stefano, Vollaro, additional, Mauro, Zaffaroni, additional, Mauro, Zampolini, additional, Roberto, Zarbo Ignazio, additional, Antonio, Zito, additional, and Luigi, Zuliani, additional

Published
2022
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24. Occurrence of hyperventilation-induced high amplitude rhythmic slowing with altered awareness after successful treatment of typical absence seizures and a network hypothesis

Author

Denis Roberto, Susanna Casellato, Antonella Coniglio, Giovanni M. Luzzu, S. Sonia Muzzu, Simone Mattozzi, Stefano Sotgiu, Maria Fadda, Alessandra Carta, Gian Luca Pruneddu, Maria Alessandra Sotgiu, Silvia Dell’Avvento, Delia M. Simula, and Caterina Cerminara

Subjects
Alkalosis, Case Report, Neurosciences. Biological psychiatry. Neuropsychiatry, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Rhythm, Typical absence, Physiology (medical), Hyperventilation, medicine, Ictal, HIHARS, Typical absence seizure, High amplitude, business.industry, Loss of awareness, food and beverages, 030208 emergency & critical care medicine, medicine.disease, Electrophysiology, Neurology, Neurology (clinical), medicine.symptom, business, Neuroscience, 030217 neurology & neurosurgery, RC321-571
Abstract

Highlights • We show that typical absence seizures (AS) and hyperventilation-induced high amplitude rhythmic slowing (HIHARS) or HIHARS with Altered Awareness (HIHARSAA) can coexist in the same patient, but never at the same time. • We found that alkalosis and dysfunction of the same neural network are involved in both AS and HIHARS. • AS and HIHARS should be better recognized to avoid misdiagnosis and overtreatment. • AS and HIHARS can coexist in the same patient, but never at the same time., Background Typical absence seizures (AS) are epileptic phenomena typically appearing in children 4–15 years of age and can be elicited by hyperventilation (HV). Hyperventilation-induced high-amplitude rhythmic slowing (HIHARS) represents a paraphysiological response during HV and may manifest with alteration of awareness (HIHARSAA). To date, HIHARSAA has mostly been described in patients without epilepsy. Aim To describe five patients with treatment-responsive typical AS who, after becoming seizure free, presented with HIHARSAA. Methods By using video-electroencephalographic recording (Video-EEG), we describe differential clinical characteristics and ictal electrophysiological patterns of both typical AS and HIHARSAA. Results We demonstrate that when HIHARSAA occurs in patients with typical AS there is a temporal window between the two phenomena. This suggests that the presence of typical AS precludes the appearance of HIHARSAA. Conclusions We hypothesize that alkalosis and dysfunction of the same neural network are involved in both typical AS and HIHARSAA and that their distinct electroclinic manifestations are due to the involvement of different ion channels. Significance A better understanding of the characteristics of typical AS and HIHARSAA and of the role of alkalosis in both, can help avoiding misdiagnosis and identifying more suitable therapies for typical AS.

Published
2021

25. CRISIS AFAR: An International Collaborative Study of the Impact of the COVID-19 Pandemic on Youth with Autism and Neurodevelopmental Conditions

Author

Bethany Vibert, Patricia Segura, Louise Gallagher, Stelios Georgiades, Panagiota Pervanidou, Audrey Thurm, Lindsay Alexander, Evdokia Anagnostou, Yuta Aoki, Catherine S.N. Birken, Somer L. Bishop, Jessica Boi, Carmela Bravaccio, Helena Brentani, Paola Canevini, Alessandra Carta, Alice Charach, Antonella Costantino, Katherine T. Cost, Elaine Andrade Cravo, Jennifer Crosbie, Chiara Davico, Alessandra Gabellone, Federica Donno, Junya Fujino, Cristiane Tezzari Geyer, Tomoya Hirota, Stephen Kanne, Makiko Kawashima, Elizabeth Kelley, Hosanna Kim, Young Shin Kim, So Hyun (Sophy) Kim, Daphne J. Korczak, Meng-Chuan Lai, Lucia Margari, Gabriele Masi, Lucia Marzulli, Luigi Mazzone, Jane McGrath, Suneeta Monga, Paola Morosini, Shinichiro Nakajima, Antonio Narzisi, Rob Nicolson, Aki Nikolaidis, Yoshihiro Noda, Kerri Nowell, Miriam Polizzi, Joana Portolese, Maria Pia Riccio, Manabu Saito, Anish K. Simhal, Martina Siracusano, Stefano Sotgiu, Jacob Stroud, Fernando Sumiya, Ida Schwartz, Yoshiyuki Tachibana, Nicole Takahashi, Riina Takahashi, Hiroki Tamon, Raffaella Tancredi, Benedetto Vitiello, Alessandro Zuddas, Bennett Leventhal, Kathleen Merikangas, Michael P Milham, and Adriana Di Martino

Abstract

ImportanceHeterogeneous mental health outcomes during the COVID-19 pandemic are recognized in the general population, but it has not been systematically assessed in youth with neurodevelopmental disorders (NDD), including autism spectrum (ASD).ObjectiveIdentify subgroups of youth with ASD/NDD based on the pandemic impact on symptoms and service changes, as well as predictors of outcomes.Design, Setting, and ParticipantsThis is a naturalistic observational study conducted across 14 North American and European clinical and/or research sites. Parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) adapted for Autism and Related Neurodevelopmental Conditions (AFAR) were cross-sectionally collected from April to October 2020. The sample included 1275, 5-21 year-old youth with ASD and/or NDD who were clinically well-characterized prior to the pandemic.Main Outcomes and MeasuresTo identify impact subgroups, hierarchical clustering analyzed eleven AFAR factors measuring pre- to pandemic changes in clinically relevant symptoms and service access. Random forest classification assessed the relative contribution in predicting subgroup membership of 20 features including socio-demographics, pre-pandemic service, and clinical severity along with indices of COVID-19 related experiences and environments empirically-derived from AFAR parent responses and global open sources.ResultsClustering analyses revealed four ASD/NDD impact subgroups. One subgroup - broad symptom worsening only (20% of the aggregate sample) - included youth with worsening symptoms that were above and beyond that of their ASD/NDD peers and with similar service disruptions as those in the aggregate average. The three other subgroups showed symptom changes similar to the aggregate average but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Pre-pandemic factors (e.g., number of services), pandemic environments and experiences (e.g., COVID-19 cases, related restrictions, COVID-19 Worries), and age emerged in unique combinations as distinct protective or risk factors for each subgroup. Together they highlighted the role of universal risk factors, such as risk perception, and the protective role of services before and during the pandemic, in middle childhood.Conclusions and RelevanceConcomitant assessment of changes in both symptoms and services access is critical to understand heterogeneous impact of the pandemic on ASD/NDD youth. It enabled the delineation of pathways to risk and resilience that include universal and ASD/NDD specific contributors.

Published
2022

26. Le disposizioni sui comuni per il 2021: una rassegna normativa nella fase di ripresa del Paese

Author

Romano Astolfo, Danilo Ballanti, Barbara Becchi, Gioacchino Benfante, Chiara Bergonzini, Paolo Brambilla, Valeria Bucci, Noemi Ilaria Buonsante, Rebeca C. Cabrera Rivera, Stefano Campostrini, Natalina Teresa Capua, Giovanna Colombini, Giovanni Carrosio, Elisa Cavasino, Fausto Corradin, Filippo Corradini, Michele Costola, Marzia De Donno, Silvia Degli Angeli, Marcello Degni, Elena di Carpegna Brivio, Cristina Equizzi, Giancarlo Ferrara, Andrea Ferri, Fabio Fiorillo, Giaime Gabrielli, Giampiero Maria Gallo, Elena Giovannini, Carla Golfieri, Raffaele Lagravinese, Eleonora Luciani, Chiara Mancini, Vanessa Manzetti, Silvia Martini, Marco Mastracci, Manuela Lucia Mei, Edoardo Meneghelli, Pasquale Mennuti, Elvina Merkaj, Larysa Minzyuk, Francesco Monaco, Andrea Morgia, Riccardo Mussari, Emanuele Padovani, Massimo Paradiso, Francesco Porcelli, Stefania Porchia, Stefano Pozzoli, Cristina Randi, Paolo Ravaioli, Giuliano Resce, Alberto Scheda, Giulia Valeria Sonzogno, Stefano Sotgiu, Marco Stradiotto, Elena Torri, Claudia Tubertini, Cesare Vignocchi, Flaviano Zandonai, Maristella Zantedeschi., Degni, M, Luciani, E, Luciani, E., Romano Astolfo, Danilo Ballanti, Barbara Becchi, Gioacchino Benfante, Chiara Bergonzini, Paolo Brambilla, Valeria Bucci, Noemi Ilaria Buonsante, Rebeca C. Cabrera Rivera, Stefano Campostrini, Natalina Teresa Capua, Giovanna Colombini, Giovanni Carrosio, Elisa Cavasino, Fausto Corradin, Filippo Corradini, Michele Costola, Marzia De Donno, Silvia Degli Angeli, Marcello Degni, Elena di Carpegna Brivio, Cristina Equizzi, Giancarlo Ferrara, Andrea Ferri, Fabio Fiorillo, Giaime Gabrielli, Giampiero Maria Gallo, Elena Giovannini, Carla Golfieri, Raffaele Lagravinese, Eleonora Luciani, Chiara Mancini, Vanessa Manzetti, Silvia Martini, Marco Mastracci, Manuela Lucia Mei, Edoardo Meneghelli, Pasquale Mennuti, Elvina Merkaj, Larysa Minzyuk, Francesco Monaco, Andrea Morgia, Riccardo Mussari, Emanuele Padovani, Massimo Paradiso, Francesco Porcelli, Stefania Porchia, Stefano Pozzoli, Cristina Randi, Paolo Ravaioli, Giuliano Resce, Alberto Scheda, Giulia Valeria Sonzogno, Stefano Sotgiu, Marco Stradiotto, Elena Torri, Claudia Tubertini, Cesare Vignocchi, Flaviano Zandonai, Maristella Zantedeschi., Degni, M, Luciani, E, and Luciani, E.

Published
2022

27. Chronic immune sensory polyradiculopathy (CISP): First juvenile case description

Author

Eduardo Nobile-Orazio, G Puseddu, Pietro Emiliano Doneddu, Alessandra Carta, A Minutolo, and Stefano Sotgiu

Subjects
Pathology, medicine.medical_specialty, Neurology, business.industry, Motor nerve, Polyradiculoneuropathy, Sensory system, Dermatology, General Medicine, medicine.disease, Polyradiculopathy, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Sensory ataxia, medicine.anatomical_structure, Somatosensory evoked potential, medicine, 030212 general & internal medicine, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, Sensory nerve
Abstract

In its typical presentation, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) occurs more often in old males as a progressive/recurrent motor and sensory nerve dysfunction with tendon areflexia. However, CIDP has also atypical clinical presentations, including pure sensory neuropathies, among which chronic immune sensory polyradiculopathy (CISP) accounts for only 0.5% of all CIDP, with no juvenile cases reported as yet. A 17-year-old girl presented for a progressive sensory ataxia and hands clumsiness. Diffuse tendon areflexia and hypokinaesthesia were observed. Motor and sensory nerve conduction studies were normal. F-waves were normal in median nerves and elongated in tibial nerves. H-reflex and somatosensory evoked potentials (SSEP) were absent. CSF normal cellularity with hyperproteinorrachia was found. Paraneoplastic, metabolic, and paraproteinemic neuropathies were excluded. A diagnosis of CISP has been made based on the presence of pure sensory symptoms in a polyneuropathic distribution, normal peripheral nerve conduction studies, and two supportive criteria (SSEP and CSF). Our paper describes the first CISP case in the pediatric age. We confirm SSEP and CSF as useful complementary tests for this diagnosis also at this age and suggest that clinicians should consider CISP in the spectrum of sporadic sensory ataxias of the pediatric age. We also suggest that in the presence of normal F-wave and peripheral motor nerve conduction, an absent H-reflex can further substantiate SSEPs in the diagnosis of CISP. Intravenous immunoglobulins were rapidly effective and safe.

Published
2020

28. Vitamin D Receptor Polymorphisms Associated with Autism Spectrum Disorder

Author

Alessandra Carta, Oscar Fumagalli, Andrea Saul Costa, Milena Zanzottera, Mario Clerici, Cristina Agliardi, Michela Zanette, Chiara Rogantini, Nasser M Al Daghri, Franca Rosa Guerini, Elisabetta Bolognesi, Matteo Chiappedi, Stefano Sotgiu, Maria Martina Mensi, and Alessandro Ghezzo

Subjects
Male, medicine.medical_specialty, Genotype, TaqI, Autism Spectrum Disorder, VDR polymorphisms, Single-nucleotide polymorphism, Calcitriol receptor, vitamin D deficiency, 03 medical and health sciences, chemistry.chemical_compound, Autistic Spectrum Disorder, Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, 0302 clinical medicine, Internal medicine, mental disorders, medicine, Vitamin D and neurology, Humans, Genetic Predisposition to Disease, 0501 psychology and cognitive sciences, Vitamin D, Child, Alleles, Genetics (clinical), Polymorphism, Genetic, VDR FokI, biology, business.industry, General Neuroscience, 05 social sciences, Immune system, VDR FokI, medicine.disease, FokI, Immune system, Endocrinology, Haplotypes, Italy, chemistry, Childhood Autism Rating Scale, biology.protein, Receptors, Calcitriol, Autism, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, 050104 developmental & child psychology
Abstract

Vitamin D is endowed with a number of biological properties, including down-regulation of inflammation, and might contribute to the pathogenesis of autism spectrum disorders (ASD). Vitamin D binds to the vitamin D Receptor (VDR); the biological activity of the ensuing complex depends on VDR FokI, BsmI, ApaI, and TaqI gene polymorphisms. We evaluated such Single Nucletoide Polymorphismsm (SNPs) in a cohort of 100 Italian families with ASD children. FokI genotype distribution was skewed in ASD children compared with their healthy sibs (Pc = 0.03 2 df) and to a group of 170 Italian healthy women (HC) (Pc = 0.04 2 df). FokI genotype and allelic distribution skewing were also observed in mothers of ASD children compared to HC (Pc = 0.04 2 df). Both Transmission Disequilibrium Test for single loci and haplotype analysis distribution revealed a major FokI (C) allele-mediated protective effect, which was more frequently transmitted (73%) than not transmitted to healthy sibs (P = 0.02). A protective FokI-, BsmI-, ApaI-, and TaqI (CCAG) haplotype was more frequently carried by healthy sibs than by ASD children (P = 1 × 10-4 ; OR: 0.1, 95% CI: 0.03-0.4) too. Finally, a strong gene-dose association of FokI (T) allele with both higher Childhood Autism Rating Scale score (Pc = 0.01) and, particularly, with hyperactivity behavior (Pc = 0.006) emerged in ASD children. Because the protein produced by the FokI (T) allele is transcriptionally less active than that produced by the FokI (C) allele, the reduced biological activity of the vitamin D/VDR complex prevalent in ASD could favor ASD- and maternal immune activation- associated inflammation. Vitamin D supplementation might be useful in preventative and rehabilitation protocols for ASD. Autism Res 2020, 13: 680-690. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Vitamin D deficiency and Vitamin D receptor (VDR) polymorphisms are associated with structural and functional brain abnormalities and behavioral disorders. We analyzed the association of VDR gene polymorphisms in a cohort of 100 Italian families with ASD children. A strong correlation between one of the VDR polymorphisms and hyperactivity behavior was evidenced in ASD children. In healthy mothers, the same VDR polymorphism was also correlated with an increased risk of giving birth to children with ASD.

Published
2020

29. Hashimoto encephalopathy in the 21st century

Author

Stefano Sotgiu, Albert Saiz, Makoto Hara, Domingo Escudero, Helena Ariño, Lidia Sabater, Thaís Armangue, Takahiro Iizuka, Francesc Graus, Mateus Mistieri Simabukuro, Josep Dalmau, and Simone Mattozzi

Subjects
0301 basic medicine, Autoimmune encephalitis, medicine.medical_specialty, biology, business.industry, Limbic encephalitis, Encephalopathy, Status epilepticus, medicine.disease, Gastroenterology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Thyroid peroxidase, Internal medicine, medicine, Etiology, biology.protein, Euthyroid, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, Encephalitis
Abstract

ObjectiveTo report the presenting syndromes and to determine whether pretreatment criteria of Hashimoto encephalopathy (HE) predict response to steroids.MethodsWe assessed symptoms and steroid responsiveness in 24 patients with pretreatment criteria of HE, including (1) subacute onset of cognitive impairment, psychiatric symptoms, or seizures; (2) euthyroid status or mild hypothyroidism; (3) serum thyroid peroxidase antibodies (TPOAb) >200 IU/mL; (4) absent neuronal antibodies in serum/CSF; and (5) no other etiologies. Additional studies included determination of TPOAb (>200 IU/mL) in 74 patients with criteria of possible autoimmune encephalitis (AE) without neuronal antibodies and 205 patients with different neuroimmunologic diseases, psychosis, or new-onset refractory status epilepticus (NORSE). Serum antibodies to the amino (ΝΗ2)-terminal of α-enolase (NH2-α-enolaseAb) were examined in the indicated 24 patients and 13 controls.ResultsThe 24 patients (14 women) with suspected HE had a median age of 48 years (range 8–79 years). Four syndromes were identified: psychiatric (7, 29%), encephalopathy (7, 29%), NORSE-like (6, 25%), and limbic encephalitis (4, 17%). Only 6 of 19 (31.6%) patients completely responded to steroids. The frequency of TPOAb in the 74 patients with possible AE (6 of 74, 8.1%) was similar to that of the 205 controls (17 of 205, 8.2%; p = 0.84). NH2-α-enolaseAb were identified in 1 of 24 suspected HE cases and 1 of 13 controls.ConclusionCurrent pretreatment criteria of HE do not predict steroid responsiveness. The detection of TPOAb across all control groups reveals their poor disease-specificity. NH2-α-enolaseAb did not help in the diagnosis of HE. These findings imply a redefinition of HE that requires a systematic exclusion of antibody-mediated encephalitis.

Published
2019

31. HLA-G allelic distribution in Sardinian children with Autism spectrum disorders: A replication study

Author

Alessandro Ghezzo, Andrea Saul Costa, Milena Zanzottera, Stefano Sotgiu, Umberto Balottin, Claudia Clerici, Matteo Chiappedi, Alessandra Carta, Mario Clerici, Elisabetta Bolognesi, Maria Paola Canevini, Maria Martina Mensi, Michela Zanette, Franca Rosa Guerini, and Cristina Agliardi

Subjects
Adult, Male, 0301 basic medicine, Genotype, Autism Spectrum Disorder, Immunology, Population, Genes, MHC Class I, Locus (genetics), Human leukocyte antigen, Biology, Cohort Studies, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Gene Frequency, HLA-G, mental disorders, Ethnicity, medicine, Humans, Genetic Predisposition to Disease, Allele, Child, education, Alleles, HLA-G Antigens, Genetics, education.field_of_study, Polymorphism, Genetic, Endocrine and Autonomic Systems, Exons, medicine.disease, 030104 developmental biology, Haplotypes, Italy, Autism spectrum disorder, Cohort, Autism, Female, 030217 neurology & neurosurgery
Abstract

Recent results show that in mainland Italian children with Autism spectrum disorder (ASD), HLA-G coding alleles distribution is skewed and an association between HLA-G*01:05N and ASD is present. Herein, in an independent cohort of Sardinian ASD (sASD) children and their relatives, we verify whether HLA-G allele association with ASD could be confirmed in this genetically peculiar insular population. One hundred children with a diagnosis of ASD, born in Sardinia and of Sardinian descent, 91 of their mothers, and 40 of their healthy siblings were enrolled. DNA sequencing analysis of HLA-G exon 2, 3 and 4 was used to obtain HLA-G allelic frequencies. Alleles distribution was compared with that of continental ASD children and with a control group of Caucasoid couples of multiparous women and their partners from Brazil and Denmark. Skewing of HLA-G allele distribution was replicated in sASD children; in particular, the HLA-G*01:03 allele, associated with reduced fetal tolerogenicity and development of myeloid leukemia, was more common in both ASD groups compared to controls (pc = 1 × 10−3; OR:3.5, 95%CI: 1.8–6.8). However, given the lack of data on HLA-G*01:03 allelic distribution among Sardinian healthy subjects, we cannot exclude a population effect. These data confirm an association of HLA-G locus with ASD development, particularly with those alleles linked to a lower expression of tolerogenic HLA-G protein, thus warranting further studies on HLA-G polymorphism distribution in different ASD populations.

Published
2019

32. VARS2-linked mitochondrial encephalopathy: two case reports enlarging the clinical phenotype

Author

Delia M. Simula, Susanna Casellato, Anna Eusebi, Alessandra Carta, Claudia Nesti, Chiara Begliuomini, Filippo M. Santorelli, Stefano Sotgiu, Veronica Dessì, Maja Di Rocco, Federica Deodato, Giorgio Magli, Denise Cassandrini, and Daria Diodato

Subjects
0301 basic medicine, lcsh:Internal medicine, Muscle Hypotonia, lcsh:QH426-470, Valine-tRNA Ligase, Developmental delay, Case Report, 030105 genetics & heredity, medicine.disease_cause, Bioinformatics, 03 medical and health sciences, Epilepsy, HLA Antigens, Mitochondrial Encephalomyopathies, VARS2, Genetics, Medicine, Humans, Spasticity, Child, lcsh:RC31-1245, Genetics (clinical), Mutation, business.industry, Epileptic encephalopathy, Homozygote, Electroencephalography, medicine.disease, Phenotype, Magnetic Resonance Imaging, Human genetics, Mitochondrial disorder, lcsh:Genetics, 030104 developmental biology, Mitochondrial respiratory chain, Child, Preschool, Cerebellar atrophy, Female, medicine.symptom, business
Abstract

Background Mitochondrial respiratory chain consists of five complexes encoded by nuclear and mitochondrial genomes. Mitochondrial aminoacyl-tRNA synthetases are key enzymes in the synthesis of such complexes. Bi-allelic variants of VARS2, a nuclear gene encoding for valyl-tRNA (Val-tRNA) synthetase, are associated to several forms of mitochondrial encephalopathies or cardiomyoencephalopathies. Among these, the rare homozygous c.1100C > T (p.Thr367Ile) mutation variably presents with progressive developmental delay, axial hypotonia, limbs spasticity, drug-resistant epilepsy leading, in some cases, to premature death. Yet only six cases, of which three are siblings, harbouring this homozygous mutation have been described worldwide. Case presentation Hereby, we report two additional cases of two non-related young girls from Sardinia, born from non-consanguineous and healthy parents, carrying the aforesaid homozygous VARS2 variant. At onset both the patients presented with worsening psychomotor delay, muscle hypotonia and brisk tendon reflexes. Standard genetic tests were normal, as well as metabolic investigations. Brain MRI showed unspecific progressive abnormalities, such as corpus callosum hypoplasia (patient A) and cerebellar atrophy (patient A and B). Diagnosis was reached by adopting massive parallel next generation sequencing. Notably clinical phenotype of the first patient appears to be milder compared to previous known cases. The second patient eventually developed refractory epilepsy and currently presents with severe global impairment. Because no specific treatment is available as yet, both patients are treated with supporting antioxidant compounds along with symptomatic therapies. Conclusions Given the paucity of clinical data about this very rare mitochondrial encephalopathy, our report might contribute to broaden the phenotypic spectrum of the disorder. Moreover, noteworthy, three out of five pedigrees so far described belong to the Northern Sardinia ethnicity.

Published
2019

33. Long-term trajectory of acquired demyelinating syndrome and multiple sclerosis in children

Author

Ignazio Roberto Zarbo, Veronica Dessì, Stefano Sotgiu, Giovanni Sotgiu, Pietro Zara, Francesca Salis, Alessandra Carta, Anna Eusebi, Valentina Pes, and Silvia Festa

Subjects
Male, 030506 rehabilitation, Pediatrics, medicine.medical_specialty, Multiple Sclerosis, Time Factors, Adolescent, Population, Annual incidence, 03 medical and health sciences, 0302 clinical medicine, Developmental Neuroscience, medicine, Prevalence, Humans, education, Child, Retrospective Studies, education.field_of_study, business.industry, Multiple sclerosis, Incidence (epidemiology), Incidence, Infant, Retrospective cohort study, Syndrome, medicine.disease, Italy, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, Neurology (clinical), 0305 other medical science, business, Very high risk, 030217 neurology & neurosurgery, Demyelinating Diseases
Abstract

AIM We assessed the frequency, characteristics, and future trajectory of monophasic acquired demyelinating syndromes (ADS) associated with conversion to paediatric multiple sclerosis. METHOD This was a retrospective observational study of Sardinian children (

Published
2021

34. SARS-CoV-2 serology after COVID-19 in multiple sclerosis: An international cohort study

Author

Maria Pia Sormani, Irene Schiavetti, Doriana Landi, Luca Carmisciano, Nicola De Rossi, Cinzia Cordioli, Lucia Moiola, Marta Radaelli, Paolo Immovilli, Marco Capobianco, Vincenzo Brescia Morra, Maria Trojano, Gioacchino Tedeschi, Giancarlo Comi, Mario Alberto Battaglia, Francesco Patti, Yara Dadalti Fragoso, Sedat Sen, Aksel Siva, Roberto Furlan, Marco Salvetti, Gianmarco Abbadessa, Umberto Aguglia, Lia Allegorico, Rossi Beatrice Maria Allegri, Maria Pia Amato, Pietro Annovazzi, Carlo Antozzi, Lucia Appendino, Sebastiano Arena, Viola Baione, Roberto Balgera, Valeria Barcella, Damiano Baroncini, Caterina Barrilà, Mario A. Battaglia, Alessandra Bellacosa, Gianmarco Bellucci, Roberto Bergamaschi, Valeria Bergamaschi, Daiana Bezzini, Beatrice Biolzi, Alvino Bisecco, Simona Bonavita, Giovanna Borriello, Chiara Bosa, Antonio Bosco, Francesca Bovis, Marco Bozzali, Laura Brambilla, Morra Vincenzo Brescia, Giampaolo Brichetto, Maria Buccafusca, Elisabetta Bucciantini, Sebastiano Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano Calabrese, Francesca Calabria, Francesca Caleri, Federico Camilli, Luisa Maria Caniatti, Roberto Cantello, Ruggero Capra, Rocco Capuano, Patrizia Carta, Paola Cavalla, Maria Grazia Celani, Maria Cellerino, Raffaella Cerqua, Clara Chisari, Raffaella Clerici, Marinella Clerico, Eleonora Cocco, Gaia Cola, Paolo Confalonieri, Antonella Conte, Marta Zaffira Conti, Christian Cordano, Susanna Cordera, Francesco Corea, Claudio Correale, Salvatore Cottone, Francesco Crescenzo, Erica Curti, Alessandro d’Ambrosio, Emanuele D’Amico, Maura Chiara Danni, Alessia d’Arma, Vincenzo Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Stefano, Marco Della Cava, Mario di Napoli, Alessia Di Sapio, Renato Docimo, Anna Dutto, Luana Evangelista, Salvatore Fanara, Diana Ferraro, Maria Teresa Ferrò, Massimo Filippi, Cristina Fioretti, Mario Fratta, Jessica Frau, Marzia Fronza, Alberto Gajofatto, Antonio Gallo, Paolo Gallo, Claudio Gasperini, Anna Ghazaryan, Bruno Giometto, Francesca Gobbin, Flora Govone, Franco Granella, Erica Grange, Maria Grazia Grasso, Angelica Guareschi, Clara Guaschino, Simone Guerrieri, Donata Guidetti, Pietro Iaffaldano, Antonio Ianniello, Luigi Iasevoli, Daniele Imperiale, Maria Teresa Infante, Matilde Inglese, Rosa Iodice, Aniello Iovino, Giovanna Konrad, Roberta Lanzillo, Caterina Lapucci, Luigi Lavorgna, Rita L’Episcopo Maria, Serena Leva, Giuseppe Liberatore, Marianna Lo Re, Marco Longoni, Leonardo Lopiano, Lorena Lorefice, Matteo Lucchini, Giacomo Lus, Davide Maimone, Maria Malentacchi, Giulia Mallucci, Simona Malucchi, Chiara Rosa Mancinelli, Luca Mancinelli, Paolo Manganotti, Teresa Giorgia Maniscalco, Vittorio Mantero, Sabrina Marangoni, Damiano Marastoni, Alessandra Girolama Marfia, Fabiana Marinelli, Alessandro Marti, Filippo Martinelli Boneschi, Federco Masserano Zoli, Francesca Matta, Laura Mendozzi, Giuseppe Meucci, Silvia Miante, Giuseppina Miele, Eva Milano, Massimiliano Mirabella, Rosanna Missione, Marcello Moccia, Sara Montepietra, Margherita Monti Bragadin, Federico Montini, Roberta Motta, Raffaele Nardone, Carolina Gabri Nicoletti, Eduardo Nobile-Orazio, Agostino Nozzolillo, Marco Onofrj, Riccardo Orlandi, Anna Palmieri, Damiano Paolicelli, Livia Pasquali, Luisa Pastò, Elisabetta Pedrazzoli, Paola Perini, Ilaria Pesci, Maria Petracca, Alfredo Petrone, Carlo Piantadosi, Anna M. Pietroboni, Federica Pinardi, Marta Ponzano, Emilio Portaccio, Mattia Pozzato, Carlo Pozzilli, Luca Prosperini, Alessandra Protti, Paolo Ragonese, Sarah Rasia, Sabrina Realmuto, Anna Repice, Eleonora Rigoni, Maria Teresa Rilla, Francesca Rinaldi, Calogero Marcello Romano, Marco Ronzoni, Marco Rovaris, Francesca Ruscica, Loredana Sabattini, Giuseppe Salemi, Lorenzo Saraceno, Alessia Sartori, Arianna Sartori, Elvira Sbragia, Cinzia Scandellari, Ilaria Scarano Giuditta, Valentina Scarano, Valentina Schillaci, Maria Sessa, Caterina Sgarito, Grazia Sibilia, Gabriele Siciliano, Alessio Signori, Elisabetta Signoriello, Leonardo Sinisi, Francesca Sireci, Patrizia Sola, Claudio Solaro, Stefano Sotgiu, Maddalena Sparaco, Maria Laura Stromillo, Silvia Strumia, Laura Emanuela Susani, Giulietta Tabiadon, Francesco Teatini, Valentina Tomassini, Simone Tonietti, Clerici Valentina Torri, Carla Tortorella, Simona Toscano, Rocco Totaro, Maria Trotta, Gabriella Turano, Monica Ulivelli, Manzo Valentino, Giovanna Vaula, Domizia Vecchio, Marco Vercellino, Elena Pinuccia Verrengia, Marika Vianello, Eleonora Virgilio, Francesca Vitetta, Stefano Vollaro, Mauro Zaffaroni, Mauro Zampolini, Ignazio Roberto Zarbo, Antonio Zito, Luigi Zuliani, Sormani, M. P., Schiavetti, I., Landi, D., Carmisciano, L., De Rossi, N., Cordioli, C., Moiola, L., Radaelli, M., Immovilli, P., Capobianco, M., Brescia Morra, V., Trojano, M., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Fragoso, Y. D., Sen, S., Siva, A., Furlan, R., Salvetti, M., Bisecco, Alvino, Pia Sormani, Maria, Schiavetti, Irene, Landi, Doriana, Carmisciano, Luca, De Rossi, Nicola, Cordioli, Cinzia, Moiola, Lucia, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, Brescia Morra, Vincenzo, Trojano, Maria, Tedeschi, Gioacchino, Comi, Giancarlo, Alberto Battaglia, Mario, Patti, Francesco, Dadalti Fragoso, Yara, Sen, Sedat, Siva, Aksel, Furlan, Roberto, Salvetti, Marco, Study Group Gianmarco Abbadessa, MuSC-19, Aguglia, Umberto, Allegorico, Lia, Beatrice Maria Allegri, Rossi, Pia Amato, Maria, Annovazzi, Pietro, Antozzi, Carlo, Appendino, Lucia, Arena, Sebastiano, Baione, Viola, Balgera, Roberto, Barcella, Valeria, Baroncini, Damiano, Barrilà, Caterina, A Battaglia, Mario, Bellacosa, Alessandra, Bellucci, Gianmarco, Bergamaschi, Roberto, Bergamaschi, Valeria, Bezzini, Daiana, Biolzi, Beatrice, Bonavita, Simona, Borriello, Giovanna, Bosa, Chiara, Bosco, Antonio, Bovis, Francesca, Bozzali, Marco, Brambilla, Laura, Vincenzo Brescia, Morra, Brichetto, Giampaolo, Buccafusca, Maria, Bucciantini, Elisabetta, Bucello, Sebastiano, Chiara Buscarinu, Maria, Paola Cabboi, Maria, Calabrese, Massimiliano, Calabria, Francesca, Caleri, Francesca, Camilli, Federico, Maria Caniatti, Luisa, Cantello, Roberto, Capra, Ruggero, Capuano, Rocco, Carta, Patrizia, Cavalla, Paola, Grazia Celani, Maria, Cellerino, Maria, Cerqua, Raffaella, Chisari, Clara, Clerici, Raffaella, Clerico, Marinella, Cocco, Eleonora, Cola, Gaia, Confalonieri, Paolo, Conte, Antonella, Zaffira Conti, Marta, Cordano, Christian, Cordera, Susanna, Corea, Francesco, Correale, Claudio, Cottone, Salvatore, Crescenzo, Francesco, Curti, Erica, D'Ambrosio, Alessandro, D'Amico, Emanuele, Chiara Danni, Maura, D'Arma, Alessia, Dattola, Vincenzo, de Biase, Stefano, De Luca, Giovanna, Federica De Mercanti, Stefania, De Mitri, Paolo, De Stefano, Nicola, Della Cava, Marco, di Napoli, Mario, Di Sapio, Alessia, Docimo, Renato, Dutto, Anna, Evangelista, Luana, Fanara, Salvatore, Ferraro, Diana, Teresa Ferrò, Maria, Filippi, Massimo, Fioretti, Cristina, Fratta, Mario, Frau, Jessica, Fronza, Marzia, Gajofatto, Alberto, Gallo, Antonio, Gallo, Paolo, Gasperini, Claudio, Ghazaryan, Anna, Giometto, Bruno, Gobbin, Francesca, Govone, Flora, Granella, Franco, Grange, Erica, Grazia Grasso, Maria, Guareschi, Angelica, Guaschino, Clara, Guerrieri, Simone, Guidetti, Donata, Iaffaldano, Pietro, Ianniello, Antonio, Iasevoli, Luigi, Imperiale, Daniele, Teresa Infante, Maria, Inglese, Matilde, Iodice, Rosa, Iovino, Aniello, Konrad, Giovanna, Lanzillo, Roberta, Lapucci, Caterina, Lavorgna, Luigi, L'Episcopo Maria, Rita, Leva, Serena, Liberatore, Giuseppe, Lo Re, Marianna, Longoni, Marco, Lopiano, Leonardo, Lorefice, Lorena, Lucchini, Matteo, Lus, Giacomo, Maimone, Davide, Malentacchi, Maria, Mallucci, Giulia, Malucchi, Simona, Rosa Mancinelli, Chiara, Mancinelli, Luca, Manganotti, Paolo, Giorgia Maniscalco, Teresa, Mantero, Vittorio, Marangoni, Sabrina, Marastoni, Damiano, Girolama Marfia, Alessandra, Marinelli, Fabiana, Marti, Alessandro, Martinelli Boneschi, Filippo, Masserano Zoli, Federco, Matta, Francesca, Mendozzi, Laura, Meucci, Giuseppe, Miante, Silvia, Miele, Giuseppina, Milano, Eva, Mirabella, Massimiliano, Missione, Rosanna, Moccia, Marcello, Montepietra, Sara, Monti Bragadin, Margherita, Montini, Federico, Motta, Roberta, Nardone, Raffaele, Gabri Nicoletti, Carolina, Nobile-Orazio, Eduardo, Nozzolillo, Agostino, Onofrj, Marco, Orlandi, Riccardo, Palmieri, Anna, Paolicelli, Damiano, Pasquali, Livia, Pastò, Luisa, Pedrazzoli, Elisabetta, Perini, Paola, Pesci, Ilaria, Petracca, Maria, Petrone, Alfredo, Piantadosi, Carlo, M Pietroboni, Anna, Pinardi, Federica, Ponzano, Marta, Portaccio, Emilio, Pozzato, Mattia, Pozzilli, Carlo, Prosperini, Luca, Protti, Alessandra, Ragonese, Paolo, Rasia, Sarah, Realmuto, Sabrina, Repice, Anna, Rigoni, Eleonora, Teresa Rilla, Maria, Rinaldi, Francesca, Marcello Romano, Calogero, Ronzoni, Marco, Rovaris, Marco, Ruscica, Francesca, Sabattini, Loredana, Salemi, Giuseppe, Saraceno, Lorenzo, Sartori, Alessia, Sartori, Arianna, Sbragia, Elvira, Scandellari, Cinzia, Scarano Giuditta, Ilaria, Scarano, Valentina, Schillaci, Valentina, Sessa, Maria, Sgarito, Caterina, Sibilia, Grazia, Siciliano, Gabriele, Signori, Alessio, Signoriello, Elisabetta, Sinisi, Leonardo, Sireci, Francesca, Sola, Patrizia, Solaro, Claudio, Sotgiu, Stefano, Sparaco, Maddalena, Laura Stromillo, Maria, Strumia, Silvia, Emanuela Susani, Laura, Tabiadon, Giulietta, Teatini, Francesco, Tomassini, Valentina, Tonietti, Simone, Valentina Torri, Clerici, Tortorella, Carla, Toscano, Simona, Totaro, Rocco, Trotta, Maria, Turano, Gabriella, Ulivelli, Monica, Valentino, Manzo, Vaula, Giovanna, Vecchio, Domizia, Vercellino, Marco, Pinuccia Verrengia, Elena, Vianello, Marika, Virgilio, Eleonora, Vitetta, Francesca, Vollaro, Stefano, Zaffaroni, Mauro, Zampolini, Mauro, Roberto Zarbo, Ignazio, Zito, Antonio, Zuliani, Luigi, Abbadessa, Gianmarco, Trotta, Maria Consiglia, and Zito, Guido Antonio

Subjects
0301 basic medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), immunosuppressive therapie, coronavirus, Settore MED/26, medicine.disease_cause, Antibodies, Viral, immunosuppressive therapies, Antibodies, Serology, Cohort Studies, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Seroepidemiologic Studies, Pandemic, Medicine, Humans, Multiple sclerosi, Viral, Coronavirus, business.industry, immunomodulatory therapie, immunomodulatory therapies, COVID-19, medicine.disease, Virology, coronaviru, Settore MED/26 - NEUROLOGIA, Sars-COV-2, 030104 developmental biology, Neurology, Neurology (clinical), business, SARS-CoV-2, Multiple Sclerosis, 030217 neurology & neurosurgery, Cohort study
Abstract

Background: The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, serological tests became routinely available. Objective: To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test. Methods: We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model. Results: Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20, p = 0.002). Conclusion: Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.

Published
2021

35. COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Author

Maria Pia Sormani, Irene Schiavetti, Luca Carmisciano, Cinzia Cordioli, Massimo Filippi, Marta Radaelli, Paolo Immovilli, Marco Capobianco, Nicola De Rossi, Giampaolo Brichetto, Eleonora Cocco, Cinzia Scandellari, Paola Cavalla, Ilaria Pesci, Antonio Zito, Paolo Confalonieri, Girolama Alessandra Marfia, Paola Perini, Matilde Inglese, Maria Trojano, Vincenzo Brescia Morra, Gioacchino Tedeschi, Giancarlo Comi, Mario Alberto Battaglia, Francesco Patti, Marco Salvetti, Gianmarco Abbadessa, Umberto Aguglia, Lia Allegorico, Beatrice Maria Allegri Rossi, Maria Pia Amato, Pietro Annovazzi, Carlo Antozzi, Lucia Appendino, Sebastiano Arena, Viola Baione, Roberto Balgera, Valeria Barcella, Damiano Baroncini, Caterina Barrilà, Alessandra Bellacosa, Gianmarco Bellucci, Roberto Bergamaschi, Valeria Bergamaschi, Daiana Bezzini, Beatrice Biolzi, Alvino Bisecco, Simona Bonavita, Giovanna Borriello, Chiara Bosa, Antonio Bosco, Francesca Bovis, Marco Bozzali, Laura Brambilla, Maria Buccafusca, Elisabetta Bucciantini, Sebastiano Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano Calabrese, Francesca Calabria, Francesca Caleri, Federico Camilli, Luisa Maria Caniatti, Roberto Cantello, Ruggero Capra, Rocco Capuano, Patrizia Carta, Maria Grazia Celani, Maria Cellerino, Raffaella Cerqua, Clara Chisari, Raffaella Clerici, Marinella Clerico, Gaia Cola, Antonella Conte, Marta Zaffira Conti, Christian Cordano, Susanna Cordera, Francesco Corea, Claudio Correale, Salvatore Cottone, Francesco Crescenzo, Erica Curti, Alessandro d'Ambrosio, Emanuele D'Amico, Maura Chiara Danni, Alessia d'Arma, Vincenzo Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Stefano, Marco Della Cava, Mario di Napoli, Alessia Di Sapio, Renato Docimo, Anna Dutto, Luana Evangelista, Salvatore Fanara, Ferraro Diana, Maria Teresa Ferrò, Cristina Fioretti, Mario Fratta, Jessica Frau, Marzia Fronza, Roberto Furlan, Alberto Gajofatto, Antonio Gallo, Paolo Gallo, Claudio Gasperini, Anna Ghazaryan, Bruno Giometto, Francesca Gobbin, Flora Govone, Franco Granella, Erica Grange, Maria Grazia Grasso, Angelica Guareschi, Clara Guaschino, Simone Guerrieri, Donata Guidetti, Pietro Iaffaldano, Antonio Ianniello, Luigi Iasevoli, Daniele Imperiale, Maria Teresa Infante, Rosa Iodice, Aniello Iovino, Giovanna Konrad, Doriana Landi, Roberta Lanzillo, Caterina Lapucci, Luigi Lavorgna, Maria Rita L'Episcopo, Serena Leva, Giuseppe Liberatore, Marianna Lo Re, Marco Longoni, Leonardo Lopiano, Lorena Lorefice, Matteo Lucchini, Giacomo Lus, Davide Maimone, Maria Malentacchi, Giulia Mallucci, Simona Malucchi, Chiara Rosa Mancinelli, Luca Mancinelli, Paolo Manganotti, Giorgia Teresa Maniscalco, Vittorio Mantero, Sabrina Marangoni, Damiano Marastoni, Fabiana Marinelli, Alessandro Marti, Filippo Martinelli Boneschi, Federco Masserano Zoli, Francesca Matta, Laura Mendozzi, Giuseppe Meucci, Silvia Miante, Giuseppina Miele, Eva Milano, Massimiliano Mirabella, Rosanna Missione, Marcello Moccia, Lucia Moiola, Sara Montepietra, Margherita MontiBragadin, Federico Montini, Roberta Motta, Raffaele Nardone, Carolina Gabri Nicoletti, Eduardo Nobile-Orazio, Agostino Nozzolillo, Marco Onofrj, Riccardo Orlandi, Anna Palmieri, Damiano Paolicelli, Livia Pasquali, Luisa Pastò, Elisabetta Pedrazzoli, Maria Petracca, Alfredo Petrone, Carlo Piantadosi, Anna M Pietroboni, Federica Pinardi, Marta Ponzano, Emilio Portaccio, Mattia Pozzato, Carlo Pozzilli, Luca Prosperini, Alessandra Protti, Paolo Ragonese, Sarah Rasia, Sabrina Realmuto, Anna Repice, Eleonora Rigoni, Maria Teresa Rilla, Francesca Rinaldi, Calogero Marcello Romano, Marco Ronzoni, Marco Rovaris, Francesca Ruscica, Loredana Sabattini, Giuseppe Salemi, Lorenzo Saraceno, Alessia Sartori, Arianna Sartori, Elvira Sbragia, Giuditta Ilaria Scarano, Valentina Scarano, Valentina Schillaci, Maria Sessa, Caterina Sgarito, Grazia Sibilia, Gabriele Siciliano, Alessio Signori, Elisabetta Signoriello, Leonardo Sinisi, Francesca Sireci, Patrizia Sola, Claudio Solaro, Stefano Sotgiu, Maddalena Sparaco, Maria Laura Stromillo, Silvia Strumia, Emanuela Laura Susani, Giulietta Tabiadon, Francesco Teatini, Valentina Tomassini, Simone Tonietti, Clerici Valentina Torri, Carla Tortorella, Simona Toscano, Rocco Totaro, Maria Trotta, Gabriella Turano, Monica Ulivelli, Manzo Valentino, Giovanna Vaula, Domizia Vecchio, Marco Vercellino, Elena Pinuccia Verrengia, Marika Vianello, Eleonora Virgilio, Francesca Vitetta, Stefano Vollaro, Mauro Zaffaroni, Mauro Zampolini, Ignazio Roberto Zarbo, Luigi Zuliani, Pia Sormani, Maria, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Filippi, Massimo, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, De Rossi, Nicola, Brichetto, Giampaolo, Cocco, Eleonora, Scandellari, Cinzia, Cavalla, Paola, Pesci, Ilaria, Zito, Guido Antonio, Confalonieri, Paolo, Alessandra Marfia, Girolama, Perini, Paola, Inglese, Matilde, Trojano, Maria, Brescia Morra, Vincenzo, Tedeschi, Gioacchino, Comi, Giancarlo, Alberto Battaglia, Mario, Patti, Francesco, Salvetti, Marco, Abbadessa, Gianmarco, Aguglia, Umberto, Allegorico, Lia, Maria Allegri Rossi, Beatrice, Pia Amato, Maria, Annovazzi, Pietro, Antozzi, Carlo, Appendino, Lucia, Arena, Sebastiano, Baione, Viola, Balgera, Roberto, Barcella, Valeria, Baroncini, Damiano, Barrilà, Caterina, Bellacosa, Alessandra, Bellucci, Gianmarco, Bergamaschi, Roberto, Bergamaschi, Valeria, Bezzini, Daiana, Biolzi, Beatrice, Bisecco, Alvino, Bonavita, Simona, Borriello, Giovanna, Bosa, Chiara, Bosco, Antonio, Bovis, Francesca, Bozzali, Marco, Brambilla, Laura, Buccafusca, Maria, Bucciantini, Elisabetta, Bucello, Sebastiano, Chiara Buscarinu, Maria, Paola Cabboi, Maria, Calabrese, Massimiliano, Calabria, Francesca, Caleri, Francesca, Camilli, Federico, Maria Caniatti, Luisa, Cantello, Roberto, Capra, Ruggero, Capuano, Rocco, Carta, Patrizia, Grazia Celani, Maria, Cellerino, Maria, Cerqua, Raffaella, Chisari, Clara, Clerici, Raffaella, Clerico, Marinella, Cola, Gaia, Conte, Antonella, Zaffira Conti, Marta, Cordano, Christian, Cordera, Susanna, Corea, Francesco, Correale, Claudio, Cottone, Salvatore, Crescenzo, Francesco, Curti, Erica, D'Ambrosio, Alessandro, D'Amico, Emanuele, Chiara Danni, Maura, D'Arma, Alessia, Dattola, Vincenzo, de Biase, Stefano, De Luca, Giovanna, Federica De Mercanti, Stefania, De Mitri, Paolo, De Stefano, Nicola, Della Cava, Marco, di Napoli, Mario, Di Sapio, Alessia, Docimo, Renato, Dutto, Anna, Evangelista, Luana, Fanara, Salvatore, Diana, Ferraro, Teresa Ferrò, Maria, Fioretti, Cristina, Fratta, Mario, Frau, Jessica, Fronza, Marzia, Furlan, Roberto, Gajofatto, Alberto, Gallo, Antonio, Gallo, Paolo, Gasperini, Claudio, Ghazaryan, Anna, Giometto, Bruno, Gobbin, Francesca, Govone, Flora, Granella, Franco, Grange, Erica, Grazia Grasso, Maria, Guareschi, Angelica, Guaschino, Clara, Guerrieri, Simone, Guidetti, Donata, Iaffaldano, Pietro, Ianniello, Antonio, Iasevoli, Luigi, Imperiale, Daniele, Teresa Infante, Maria, Iodice, Rosa, Iovino, Aniello, Konrad, Giovanna, Landi, Doriana, Lanzillo, Roberta, Lapucci, Caterina, Lavorgna, Luigi, Rita L'Episcopo, Maria, Leva, Serena, Liberatore, Giuseppe, Lo Re, Marianna, Longoni, Marco, Lopiano, Leonardo, Lorefice, Lorena, Lucchini, Matteo, Lus, Giacomo, Maimone, Davide, Malentacchi, Maria, Mallucci, Giulia, Malucchi, Simona, Rosa Mancinelli, Chiara, Mancinelli, Luca, Manganotti, Paolo, Teresa Maniscalco, Giorgia, Mantero, Vittorio, Marangoni, Sabrina, Marastoni, Damiano, Marinelli, Fabiana, Marti, Alessandro, Martinelli Boneschi, Filippo, Masserano Zoli, Federco, Matta, Francesca, Mendozzi, Laura, Meucci, Giuseppe, Miante, Silvia, Miele, Giuseppina, Milano, Eva, Mirabella, Massimiliano, Missione, Rosanna, Moccia, Marcello, Moiola, Lucia, Montepietra, Sara, Montibragadin, Margherita, Montini, Federico, Motta, Roberta, Nardone, Raffaele, Gabri Nicoletti, Carolina, Nobile-Orazio, Eduardo, Nozzolillo, Agostino, Onofrj, Marco, Orlandi, Riccardo, Palmieri, Anna, Paolicelli, Damiano, Pasquali, Livia, Pastò, Luisa, Pedrazzoli, Elisabetta, Petracca, Maria, Petrone, Alfredo, Piantadosi, Carlo, M Pietroboni, Anna, Pinardi, Federica, Ponzano, Marta, Portaccio, Emilio, Pozzato, Mattia, Pozzilli, Carlo, Prosperini, Luca, Protti, Alessandra, Ragonese, Paolo, Rasia, Sarah, Realmuto, Sabrina, Repice, Anna, Rigoni, Eleonora, Teresa Rilla, Maria, Rinaldi, Francesca, Marcello Romano, Calogero, Ronzoni, Marco, Rovaris, Marco, Ruscica, Francesca, Sabattini, Loredana, Salemi, Giuseppe, Saraceno, Lorenzo, Sartori, Alessia, Sartori, Arianna, Sbragia, Elvira, Ilaria Scarano, Giuditta, Scarano, Valentina, Schillaci, Valentina, Sessa, Maria, Sgarito, Caterina, Sibilia, Grazia, Siciliano, Gabriele, Signori, Alessio, Signoriello, Elisabetta, Sinisi, Leonardo, Sireci, Francesca, Sola, Patrizia, Solaro, Claudio, Sotgiu, Stefano, Sparaco, Maddalena, Laura Stromillo, Maria, Strumia, Silvia, Laura Susani, Emanuela, Tabiadon, Giulietta, Teatini, Francesco, Tomassini, Valentina, Tonietti, Simone, Valentina Torri, Clerici, Tortorella, Carla, Toscano, Simona, Totaro, Rocco, Trotta, Maria Consiglia, Turano, Gabriella, Ulivelli, Monica, Valentino, Manzo, Vaula, Giovanna, Vecchio, Domizia, Vercellino, Marco, Pinuccia Verrengia, Elena, Vianello, Marika, Virgilio, Eleonora, Vitetta, Francesca, Vollaro, Stefano, Zaffaroni, Mauro, Zampolini, Mauro, Roberto Zarbo, Ignazio, Zuliani, Luigi, Sormani, M. P., Schiavetti, I., Carmisciano, L., Cordioli, C., Filippi, M., Radaelli, M., Immovilli, P., Capobianco, M., De Rossi, N., Brichetto, G., Cocco, E., Scandellari, C., Cavalla, P., Pesci, I., Zito, A., Confalonieri, P., Marfia, G. A., Perini, P., Inglese, M., Trojano, M., Brescia Morra, V., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., Zito, Antonio, BRESCIA MORRA, Vincenzo, Trotta, Maria, Sormani, Maria Pia, Marfia, Girolama Alessandra, and Battaglia, Mario Alberto

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Coronavirus disease 2019 (COVID-19), Population, Intensive Care Unit, COVID-19, Cohort Studies, Comorbidity, Female, Hospitalization, Humans, Intensive Care Units, Italy, Middle Aged, Retrospective Studies, Risk Factors, Severity of Illness Index, Context (language use), Settore MED/26, Lower risk, Retrospective Studie, Internal medicine, Multiple Sclerosi, Medicine, In patient, National level, education, education.field_of_study, Expanded Disability Status Scale, business.industry, Risk Factor, Ethics committee, medicine.disease, Icu admission, Settore MED/26 - NEUROLOGIA, Neurology, Relative risk, Family medicine, Cohort, Honorarium, Observational study, Neurology (clinical), Cohort Studie, business, Human
Abstract

Background: It is unclear how multiple sclerosis (MS) affects the severity of Covid-19. Methods: Hospitalization, Intensive Care Unit (ICU) admission and death after Covid-19 diagnosis of 1362 MS patients were compared to the age and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher-risk: EDSS>3 or at least one comorbidity, lower-risk: EDSS

Published
2021

36. Expanding the Spectrum of Acute Cerebellitis due to SARS-Cov-2

Author

Roberto Antonucci, Antonello Pippia, Sergio Uzzau, Stefano Sotgiu, and Alessandra Carta

Subjects
2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, Virology, Developmental Neuroscience, Neurology, Pediatrics, Perinatology and Child Health, Humans, Medicine, Neurology (clinical), business
Published
2021

37. Juvenile Chronic Inflammatory Demyelinating Polyneuropathy Epidemiology in Sardinia, Insular Italy

Author

Veronica Dessì, Eduardo Nobile-Orazio, Pietro Emiliano Doneddu, Giorgio Magli, Alessandra Carta, Ilaria Onida, Stefano Sotgiu, Angela Nuvoli, Marta Conti, Silvia Festa, and Paolo Castiglia

Subjects
medicine.medical_specialty, Pediatrics, Neurology, Adolescent, Population, Prevalence, Chronic inflammatory demyelinating polyneuropathy, 03 medical and health sciences, Mediterranean Islands, 0302 clinical medicine, Epidemiology, medicine, Juvenile, Humans, 030212 general & internal medicine, education, Child, education.field_of_study, business.industry, Incidence (epidemiology), Incidence, Infant, Polyradiculoneuropathy, General Medicine, medicine.disease, Italy, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating, Child, Preschool, Pediatrics, Perinatology and Child Health, Practice Guidelines as Topic, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Background Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare and disabling immunomediated radiculoneuropathy. Its worldwide epidemiology is heterogeneous and, in adults, CIDP prevalence varies from 0.6 to 9 cases per 100,000 population. Juvenile CIDP (jCIDP) is even rarer, with age-specific prevalence rates varying from 0.23 to 1.26 owing to different diagnostic criteria (American Academy of Neurology [AAN] and European Federation of Neurological Societies/Peripheral Nerve Society [EFNS/PNS]), different age grouping or, genuine differences. Objectives We assessed jCIDP incidence and prevalence in Sardinia, an area at very-high risk for autoimmune diseases, using comparable methods. Design The study area was the northern Sardinia, insular Italy, with 491,571 inhabitants and a pediatric population (0–18 years) of 79,086 individuals. Results On prevalence day (December 31, 2019) the total crude, age-specific prevalence rate were 6.32 per 100,000 according with AAN criteria, 7.58 per 100,000 population with European Neuromuscular Center (ENMC) criteria, and 8.85 per 100,000 population with both 2006 and 2010 EFNS/PNS criteria. Crude mean incidence rate were 0.42 per 100,000 per year with AAN criteria, 0.50 per 100,000 per year with ENMC criteria, and 0.59 per 100,000 per year using 2006 and 2010 EFNS/PNS criteria. Of the eight patients, six had typical CIDP, one had multifocal-acquired demyelinating sensory and motor neuropathy (MADSAM), and one chronic immune sensory polyradiculopathy (CISP). Patient's disability was generally mild. Clinical course was progressive, monophasic, or relapsing. Conclusion jCIDP prevalence and incidence rates in Sardinia were criteria-dependent, the lowest obtained when using AAN criteria, the highest using the EFNS/PNS. Nonetheless, even with the exclusion of the “possible” category, by using comparable methodology, prevalence rates in Sardinia are considerably higher than the range reported in all previous jCIDP studies.

Published
2020

38. Immune regulation of neurodevelopment at the mother-foetus interface: the case of autism

Author

Elisabetta Bolognesi, Chiara Scoppola, Salvatorica Manca, Franca Rosa Guerini, Stefano Sotgiu, Alessandra Minutolo, Mario Clerici, Maria Clotilde Melis, Antonella Gagliano, Giulia Pisuttu, and Alessandra Carta

Subjects
0301 basic medicine, Immunology, Reviews, autism spectrum disorder, Disease, Review, Gene mutation, 03 medical and health sciences, 0302 clinical medicine, Neurodevelopmental disorder, Immune system, gestation, mental disorders, medicine, Immunology and Allergy, General Nursing, Tissue homeostasis, Autoimmune disease, maternal immune activation, neurodevelopment, business.industry, autoimmunity, medicine.disease, 030104 developmental biology, Autism spectrum disorder, inflammation, Autism, business, Neuroscience, 030217 neurology & neurosurgery
Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by deficits in social communication and stereotypical behaviours. ASD’s aetiology remains mostly unclear, because of a complex interaction between genetic and environmental factors. Recently, a strong consensus has developed around ASD’s immune‐mediated pathophysiology, which is the subject of this review. For many years, neuroimmunological studies tried to understand ASD as a prototypical antibody‐ or cell‐mediated disease. Other findings indicated the importance of autoimmune mechanisms such as familial and individual autoimmunity, adaptive immune abnormalities and the influence of infections during gestation. However, recent studies have challenged the idea that autism may be a classical autoimmune disease. Modern neurodevelopmental immunology shows the double‐edged nature of many immune effectors, which can be either beneficial or detrimental depending on tissue homeostasis, stressors, neurodevelopmental stage, inherited and de novo gene mutations and other variables. Nowadays, mother–child interactions in the prenatal environment appear to be crucial for the occurrence of ASD. Studies of animal maternal–foetal immune interaction are being fruitfully carried out using different combinations of type and timing of infection, of maternal immune response and foetal vulnerability and of resilience factors to hostile events. The derailed neuroimmune crosstalk through the placenta initiates and maintains a chronic foetal neuroglial activation, eventually causing the alteration of neurogenesis, migration, synapse formation and pruning. The importance of pregnancy can also allow early immune interventions, which can significantly reduce the increasing risk of ASD and its heavy social burden., In this review, we argue over the significance of the several immune signatures associated with both susceptibility to autistic disorder and susceptibility to its core social and behavioural traits. Despite conclusive evidence, an impaired mother–child immune interplay during pregnancy is thought to be aetiopathogenetically crucial for the atypical neurodevelopment as observed in autism, and an appropriate management of immune responses during pregnancy may positively impact on autism.

Published
2020

39. Paroxysmal rhythmic pelvic movements: an unusual paediatric presentation of Chiari I malformation with syringomyelia

Author

Alessandra Carta, Stefano Sotgiu, Chiara Scoppola, Francesca Salis, and Giulia Pisuttu

Subjects
medicine.medical_specialty, business.industry, General Medicine, Anatomy, medicine.disease, Magnetic Resonance Imaging, Syringomyelia, Arnold-Chiari Malformation, Rhythm, Chiari I malformation, Pediatrics, Perinatology and Child Health, Medicine, Humans, Neurology (clinical), Neurosurgery, Presentation (obstetrics), business, Child
Published
2020

40. Anti-GAD epileptic encephalopathy in a toddler with Parry-Romberg syndrome

Author

Francesc Graus, Stefano Sotgiu, Alessandro Consolaro, Paolo Picco, and Susanna Casellato

Subjects
Male, Pathology, medicine.medical_specialty, Neurology, Dermatology, Status epilepticus, Anti-GAD antibody, Autoimmune encephalopathy, Autoimmune epilepsy, Parry-Romberg syndrome, 03 medical and health sciences, 0302 clinical medicine, Facial Hemiatrophy, medicine, Humans, 030212 general & internal medicine, Autoantibodies, Epilepsy, Glutamate Decarboxylase, business.industry, Parry–Romberg syndrome, General Medicine, medicine.disease, Magnetic Resonance Imaging, Rash, Hyperintensity, Psychiatry and Mental health, Child, Preschool, Neurology (clinical), medicine.symptom, Vasculitis, business, 030217 neurology & neurosurgery, Morphea, Encephalitis
Abstract

Parry-Romberg syndrome (PRS) is a progressive facial hemiatrophy often associated with severe epilepsy. Although an immune-mediated vasculitic pathogenesis is widely assumed, no CNS-specific autoantibody has been described so far. A 2-year-old boy was admitted for a status epilepticus preceded by fever, restlessness, insomnia, and left facial rash. Cerebrospinal fluid was positive for glutamic acid decarboxylase (GAD)-antibodies. Brain MRI revealed FLAIR hyperintensities on left mediotemporal areas. He was successfully treated with intravenous methylprednisolone. One month later, seizures and facial rash reappeared and steroids were satisfactorily repeated. However, left hemifacial rash reappeared 5 months later, slowly followed by sclerotic skin lesions on frontal scalp and hemifacial sub-atrophy, leading to a diagnosis of PRS. Three years later, and despite chronic immunosuppression, new MRI lesions on left white matter are seen and left hemifacial atrophy has progressed. For the first time, we describe GAD autoantibodies in a PRS patient with epileptic encephalopathy. Epileptic syndromes with GAD autoantibodies are frequently described though with a questionable pathogenic significance. Given the clinical and MRI similarities of PRS with both Morphea and Rasmussen's encephalitis, we suggest that, in our patient, the initial facial skin vasculitis spread into CNS vessels through perforating arteries, inducing neuronal MHC-class I presentation of GAD epitopes, ultimately causing CD8-mediated neuronal cytotoxicity and the epileptic encephalopathy. GAD autoantibodies might represent the missing pathophysiological link between PRS and neuropsychiatric manifestations.

Published
2020

41. HLA-G∗14bp Insertion and the KIR2DS1-HLAC2 Complex Impact on Behavioral Impairment in Children with Autism Spectrum Disorders

Author

Umberto Balottin, Elisabetta Bolognesi, Andrea Saul Costa, Alessandro Ghezzo, Matteo Chiappedi, Franca Rosa Guerini, Cristina Agliardi, Mario Clerici, Michela Zanette, Salvatorica Manca, Milena Zanzottera, Maria Martina Mensi, and Stefano Sotgiu

Subjects
Male, 0301 basic medicine, Multifactorial Inheritance, medicine.medical_specialty, Autism Spectrum Disorder, HLA-C Antigens, Human leukocyte antigen, White People, DSM-5, Cohort Studies, 03 medical and health sciences, HLA-C, 0302 clinical medicine, INDEL Mutation, Receptors, KIR, Polymorphism (computer science), Internal medicine, HLA-G, medicine, Humans, Child, Psychiatry, HLA-G Antigens, Psychiatric Status Rating Scales, General Neuroscience, Brain, Electroencephalography, medicine.disease, 030104 developmental biology, Endocrinology, In utero, Childhood Autism Rating Scale, Autism, Female, Psychology, 030217 neurology & neurosurgery
Abstract

Activating KIR-HLA-C ligand complexes and HLA-G∗14bp insertion/deletion (+/−) polymorphism were associated to Autism Spectrum Disorders (ASD) and were suggested to correlate with inflammation during fetal development. We evaluated whether HLA-G∗14bp(+/−) and KIR-HLA-C complexes are associated with cognitive and behavioral scores and EEG profile in 119 ASD children (58 from Sardinia, 61 from Peninsular Italy). KIR2DS1-C2; KIR2DS2-C1; KIR2DL1-C2; KIR2DL2-C1; KIR2DL3-C1 and HLA-G∗14bp(+/−) were molecularly genotyped by Single Specific Primer PCR and gel electrophoresis. Univariate linear model analysis adjusted for age, gender and provenience showed statistically higher scores of Childhood Autism Rating Scale (CARS) and Autistic Core Behavior in KIR2DS1-C2 + /HLA-G∗14bp +ASD children (43.7 ± 1.5, p = 0.03; 3.3 ± 0.1, p = 0.03, respectively). These results suggested a synergistic polygenic association of KIR2DS1-HLAC2+/HLA-G∗14bp+ pattern with behavioral impairment in ASD children.

Published
2018

42. HLA-G coding region polymorphism is skewed in autistic spectrum disorders

Author

Stefano Sotgiu, Maria Martina Mensi, Elisabetta Bolognesi, Umberto Balottin, Alessandra Carta, Andrea Saul Costa, Mario Clerici, Maria Paola Canevini, Alessandro Ghezzo, Milena Zanzottera, Franca Rosa Guerini, Matteo Chiappedi, Enrico Ripamonti, Cristina Agliardi, and Michela Zanette

Subjects
Male, 0301 basic medicine, Autism Spectrum Disorder, Immunology, Human leukocyte antigen, Biology, 03 medical and health sciences, Behavioral Neuroscience, Exon, 0302 clinical medicine, Immune system, Gene Frequency, Polymorphism (computer science), HLA-G, medicine, Humans, Allele, Child, HLA-G Antigens, Pregnancy, Polymorphism, Genetic, Endocrine and Autonomic Systems, medicine.disease, 030104 developmental biology, Cohort, Female, 030217 neurology & neurosurgery
Abstract

Different isoforms of HLA-G protein are endowed with a differential ability to induce allogenic tolerance during pregnancy. As prenatal immune activation is suggested to play a role in the onset of autistic spectrum disorders (ASD), we evaluated HLA G*01:01-*01:06 allelic polymorphism in a cohort of Italian children affected by ASD (N=111) their mothers (N=81), and their healthy siblings (N=39). DNA sequencing analysis of HLA-G exon 2, 3 and 4 was used to obtain HLA-G allelic frequencies; alleles distribution was compared with that of two control groups of Caucasoid couples of multiparous women and their partners from Brazil and Denmark. HLA-G distribution was significantly different in ASD children compared to both control groups (Brazilian pc=1×10-4; Danish pc=1×10-3). Since HLA-G distribution was similar in the two control groups, their data were pooled. Results indicated that HLA-G*01:01 was significantly less frequent (pc=1×10-4; OR:0.5, 95%CI: 0.3-0.7) whereas HLA-G*01:05N was significantly more frequent (pc=2×10-3; OR:7.3, 95%CI: 2.4-26.6) in ASD children compared to combined controls. Finally, no clear pattern emerged when HLA-G allelic distribution was analyzed in healthy sibs. Notably, HLA-G allelic distribution found in ASD mothers was similar to that observed in the control subgroup of women with recurrent miscarriages, whilst it was significantly different compared to women without miscarriages (pc=6×10-4 df=12). Since HLA-G*01:01 is associated with the elicitation of KIR-mediated tolerogenic responses and HLA-G*01:05N correlates with NK cells activation, results herein indicate that an immune activating milieu during pregnancy is more likely observed in association with the development of ASD, similarly to what occurs in women with recurrent miscarriages.

Published
2018

43. Confirmation of a new phenotype in an individual with a variant in the last part of exon 30 of CREBBP

Author

Valentina Pes, Manuela Oppo, Stefano Sotgiu, Chiara Perria, Rossano Atzeni, Gianmauro Cuccuru, Andrea Angius, Paolo Uva, Gigliola Serra, Laura Crisponi, Stefano Onano, Stefania Olla, Ivana Persico, Francesco Cucca, Raoul C.M. Hennekam, APH - Quality of Care, Amsterdam Reproduction & Development (AR&D), and Paediatric Genetics

Subjects
Male, 0301 basic medicine, Adolescent, 030105 genetics & heredity, Biology, medicine.disease_cause, 03 medical and health sciences, Exon, Genetics, medicine, Humans, Missense mutation, CREB-binding protein, EP300, Genetic Association Studies, Genetics (clinical), Exome sequencing, Rubinstein-Taybi Syndrome, Mutation, Rubinstein–Taybi syndrome, Exons, Prognosis, medicine.disease, CREB-Binding Protein, Phenotype, Pedigree, 030104 developmental biology, biology.protein, Female
Abstract

We report here a novel de novo missense variant affecting the last amino acid of exon 30 of CREBBP [NM_004380, c.5170G>A; p.(Glu1724Lys)] in a 17-year-old boy presenting mild intellectual disability and dysmorphisms but not resembling the phenotype of classical Rubinstein–Taybi syndrome. The patient showed a marked overweight from early infancy on and had cortical heterotopias. Recently, 22 individuals have been reported with missense mutations in the last part of exon 30 and the beginning of exon 31 of CREBBP, showing this new phenotype. This additional case further delineates the genotype–phenotype correlations within the molecular and phenotypic spectrum of variants in CREBBP and EP300.

Published
2019

44. Exploring by whole exome sequencing patients with initial diagnosis of Rubinstein-Taybi syndrome: the interconnections of epigenetic machinery disorders

Author

Chiara Perria, Italia Loddo, Marco Seri, Milena Crippa, Stefano Sotgiu, Maria Piccione, Marina Frontali, Lidia Larizza, Elisa Biamino, Palma Finelli, Pamela Magini, Maria Chiara Gandini, Elisa Colombo, Gloria Negri, Antonella Boni, Donatella Milani, Tommaso Pippucci, Michael J. Bamshad, Deborah A. Nickerson, Joshua D. Smith, Elisabetta Di Fede, Cristina Gervasini, Giuseppina Vitiello, Negri G., Magini P., Milani D., Crippa M., Biamino E., Piccione M., Sotgiu S., Perria C., Vitiello G., Frontali M., Boni A., Di Fede E., Gandini M.C., Colombo E.A., Bamshad M.J., Nickerson D.A., Smith J.D., Loddo I., Finelli P., Seri M., Pippucci T., Larizza L., Gervasini C., Negri, Gloria, Magini, Pamela, Milani, Donatella, Crippa, Milena, Biamino, Elisa, Piccione, Maria, Sotgiu, Stefano, Perrìa, Chiara, Vitiello, Giuseppina, Frontali, Marina, Boni, Antonella, Di Fede, Elisabetta, Gandini, Maria Chiara, Colombo, Elisa Adele, Bamshad, Michael J., Nickerson, Deborah A., Smith, Joshua D., Loddo, Italia, Finelli, Palma, Seri, Marco, Pippucci, Tommaso, Larizza, Lidia, and Gervasini, Cristina

Subjects
Male, Genetic Association Studie, Compound heterozygosity, Whole Exome Sequencing, Article, Epigenesis, Genetic, 03 medical and health sciences, whole exome sequencing, Rubinstein–Taybi syndrome, epigenetic mutations, Exome Sequencing, Genetics, medicine, Humans, Epigenetics, EP300, Child, Genetics (clinical), Exome sequencing, Genetic Association Studies, 030304 developmental biology, Rubinstein-Taybi Syndrome, 0303 health sciences, Comparative Genomic Hybridization, biology, Rubinstein–Taybi syndrome, 030305 genetics & heredity, Infant, Newborn, Facies, Infant, medicine.disease, Facie, CREB-Binding Protein, Human genetics, RSTS, KMT2A, Phenotype, Child, Preschool, Mutation, biology.protein, Neurodegenerative disorders, Female, Haploinsufficiency, E1A-Associated p300 Protein, Human
Abstract

Rubinstein–Taybi syndrome (RSTS) is an autosomal-dominant neurodevelopmental disease affecting 1:125,000 newborns characterized by intellectual disability, growth retardation, facial dysmorphisms and skeletal abnormalities. RSTS is caused by mutations in genes encoding for writers of the epigenetic machinery: CREBBP (~ 60%) or its homologous EP300 (~ 10%). No causative mutation is identified in up to 30% of patients. We performed whole-exome sequencing (WES) on eight RSTS-like individuals who had normal high-resolution array CGH testing and were CREBBP- and EP300-mutation -negative, to identify the molecular cause. In four cases, we identified putatively causal variants in three genes (ASXL1, KMT2D and KMT2A) encoding members of the epigenetic machinery known to be associated with the Bohring–Opitz, Kabuki and Wiedemann–Steiner syndromes. Each variant is novel, de novo, fulfills the ACMG criteria and is predicted to result in loss-of-function leading to haploinsufficiency of the epi-gene. In two of the remaining cases, homozygous/compound heterozygous variants in XYLT2 and PLCB4 genes, respectively, associated with spondyloocular and auriculocondylar 2 syndromes and in the latter an additional candidate variant in XRN2, a gene yet unrelated to any disease, were detected, but their pathogenicity remains uncertain. These results underscore the broad clinical spectrum of Mendelian disorders of the epigenetic apparatus and the high rate of WES disclosure of the genetic basis in cases which may pose a challenge for phenotype encompassing distinct syndromes. The overlapping features of distinct intellectual disability syndromes reflect common pathogenic molecular mechanisms affecting the complex regulation of balance between open and closed chromatin.

Published
2018

45. Maternal multiple sclerosis is not a risk factor for neurodevelopmental disorders in offspring

Author

Antonella Serra, Franca Rosa Guerini, Maria Angela Biancu, Riccardo Bazzardi, Ignazio Roberto Zarbo, Alessandra Carta, Federica De Martino, Marta Conti, Chiara Scoppola, Stefano Sotgiu, Maria Clotilde Melis, and Giulia Pisuttu

Subjects
Pediatrics, medicine.medical_specialty, Offspring, autism spectrum disorder, multiple sclerosis, medicine.disease_cause, attention deficit hyperactivity/impulsivity disorder, Autoimmunity, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, 030225 pediatrics, Medicine, Specific Learning Disorder, Family history, Risk factor, Pregnancy, business.industry, Multiple sclerosis, Neurodevelopmental disorders, medicine.disease, Original Research Paper, specific learning disorders, Autism spectrum disorder, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Background Childhood neurodevelopmental disorders (NDDs), including specific learning disorders (SLD), attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are pathogenically linked to familial autoimmunity and maternal immune-mediated diseases during pregnancy. Objective We studied maternal MS as a potential risk factor for NDDs occurrence in offspring. Methods MS and control mothers were subjected to questionnaires to ascertain NDD diagnosis in their progeny and the occurrence of both autoimmune and neurodevelopment disorders in their families. Suspected NDD cases were evaluated to confirm or rule out the diagnosis. Results Of the 322 MS women, 206 (64%) have 361 children; of these, 27 (7.5%) were diagnosed with NDD (11% ADHD; 22% ASD; 67% SLD). NDD-risk in offspring was associated to family history of autoimmunity and to NDDs both in MS and non-MS mother families ( r = 0.75; p = 0.005) whereas it was not associated to maternal MS. Conclusions For the first time, we demonstrate that maternal MS does not predispose children to higher risk for NDD. On a mechanistic view, we suggest that the intrinsic organ-specific nature of MS does not impair the mother–child cross-talk in decidua nor does it influence fetal neurodevelopment.

Published
2021

46. Clinical and Neurobehavioral Features of Three Novel Kabuki Syndrome Patients with Mosaic KMT2D Mutations and a Review of Literature

Author

Dario Cocciadiferro, Natascia Malerba, Alessandra Vancini, Bartolomeo Augello, Giuseppe Merla, Francesca Romana Lepri, Valentina Pes, Bruno Dallapiccola, Antonio Novelli, Paolo Alfieri, Stefano Sotgiu, Renzo Gherardi, Cristina Caciolo, Iolanda Adipietro, Maria Cristina Digilio, Gabriella Maria Squeo, Lepri, Fr, Cocciadiferro, D, Augello, B, Alfieri, P, Pes, V, Vancini, A, Caciolo, C, Squeo, Gm, Malerba, N, Adipietro, I, Novelli, A, Sotgiu, S, Gherardi, R, Digilio, Mc, Dallapiccola, B, and Merla, G

Subjects
0301 basic medicine, KMT2D gene, Nonsense mutation, Case Report, KMT2D/MLL2, Biology, Catalysis, Frameshift mutation, Inorganic Chemistry, lcsh:Chemistry, 03 medical and health sciences, Intellectual disability, medicine, Physical and Theoretical Chemistry, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, Genetic testing, Genetics, medicine.diagnostic_test, Organic Chemistry, Chromatin modifier, General Medicine, medicine.disease, Computer Science Applications, developmental delay, kabuki syndrome, 030104 developmental biology, mosaicism, lcsh:Biology (General), lcsh:QD1-999, Kabuki syndrome
Abstract

Kabuki syndrome (KS) is a rare disorder characterized by multiple congenital anomalies and variable intellectual disability caused by mutations in KMT2D/MLL2 and KDM6A/UTX, two interacting chromatin modifier responsible respectively for 56–75% and 5–8% of the cases. To date, three KS patients with mosaic KMT2D deletions in blood lymphocytes have been described. We report on three additional subjects displaying KMT2D gene mosaics including one in which a single nucleotide change results in a new frameshift mutation (p.L1199HfsX7), and two with already-known nonsense mutations (p.R4484X and p.R5021X). Consistent with previously published cases, mosaic KMT2D mutations may result in mild KS facial dysmorphisms and clinical and neurobehavioral features, suggesting that these characteristics could represent the handles for genetic testing of individuals with slight KS-like traits.

Published
2017

47. Heavy Metals and Multiple Sclerosis in Sardinian Population (Italy)

Author

Giovanni Sotgiu, Beatrice Bocca, Giovanni Forte, Stefano Sotgiu, Andrea Montella, Maria Alessandra Sotgiu, Paola Tolu, Juan A. Marchal, and Roberto Madeddu

Subjects
Chemistry, Sardinian population, Multiple sclerosis, Biochemistry (medical), Clinical Biochemistry, Physiology, Heavy metals, medicine.disease, Biochemistry, Analytical Chemistry, Cerebrospinal fluid, Electrochemistry, medicine, Inductively coupled plasma mass spectrometry, Spectroscopy
Abstract

The understanding of factors involved in the etiopathogenesis of Multiple Sclerosis (MS) is very important, especially in Sardinia (insular Italy) where one of the highest MS incidences in the world is consistently reported over time. There is evidence that some metals are implicated in the MS course and disability, and, a study was carried out to assess the concentration of Al, Cd, Cu, Fe, Mn, Pb, and Zn in the cerebrospinal fluid (CSF) of 51 Sardinian subjects (29 consecutive patients and 22 controls). In fact, any unbalance in the homeostasis of metals in the CSF might predispose to the cellular brain metal transport and accumulation giving rise to pathogenic lesions terminating in neurodegeneration. Samples were diluted with water and metals were quantified by sector field inductively coupled plasma mass spectrometry (SF-ICP-MS). Results revealed that none of the metals quantified in the CSF were able to distinguish the MS cases from controls and the different MS forms. Furthermore, sex, age, coffee, ...

Published
2011

48. Reader response: Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: I: Fetal risks

Author

Chiara Begliuomini, Franca Rosa Guerini, Anna Eusebi, Alessandra Carta, and Stefano Sotgiu

Subjects
0301 basic medicine, Pediatrics, medicine.medical_specialty, Fetus, Pregnancy, business.industry, Multiple sclerosis, medicine.disease, Fetal exposure, behavioral disciplines and activities, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Natalizumab, Autism spectrum disorder, embryonic structures, mental disorders, Medicine, Language disorder, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Portaccio et al.1 reported that fetal exposure to natalizumab increases the risk of spontaneous abortions and congenital anomalies. The authors also described one autism spectrum disorder (ASD) and one language disorder case.

Published
2018

49. Novel reliable real-time PCR for differential detection of MSRVenv and syncytin-1 in RNA and DNA from patients with multiple sclerosis

Author

L Poddighe, Caterina Serra, Giannina Arru, Giuseppe Mameli, Stefano Sotgiu, Antonina Dolei, Giuseppe Delogu, and Vito Astone

Subjects
Adult, Male, Multiple Sclerosis, Molecular Sequence Data, Sequence Homology, Pregnancy Proteins, Polymerase Chain Reaction, law.invention, Diagnosis, Differential, chemistry.chemical_compound, Retrovirus, Viral Envelope Proteins, Western blot, law, Virology, medicine, Humans, Gene, Polymerase chain reaction, DNA Primers, Base Sequence, biology, medicine.diagnostic_test, Endogenous Retroviruses, Brain, Gene Products, env, RNA, Sequence Analysis, DNA, Middle Aged, biology.organism_classification, Molecular biology, Blood, Real-time polymerase chain reaction, chemistry, DNA, Viral, biology.protein, RNA, Viral, Female, Antibody, DNA
Abstract

Two components of the HERV-W family of human endogenous retroviruses are activated during multiple sclerosis (MS) and proposed immunopathogenic co-factors: MSRV (MS-associated retrovirus), and ERVWE1 (whose env protein, syncytin-1, reaches the plasma membrane). MSRVenv and syncytin-1 are closely related, and difficult to distinguish each other. The sequences of extracellular MSRVenv and of syncytin-1 available in GenBank were compared with those found in MS patients and controls of the cohort under study. With respect to syncytin-1, MSRVenv sequences have a 12-nucleotide insertion in the trans-membrane moiety. Based on this insertion, discriminatory real-time PCR assays were developed, that can amplify selectively either MSRVenv or syncytin-1. The data of MS patients and controls indicated that MSRV and ERVWE1 are both expressed in the brain of MS patients, while only MSRV is present in the blood; MSRV was released in culture by PBMCs of MSRV-producer individuals. These cells expressed the complete MSRVenv gene in the absence of syncytin-1 expression, up to the final, fully glycosylated envelope protein product, since western blot staining with anti-HERV-Wenv antibody detected two bands of the same molecular weight (73 and 61 kDa) of the fully glycosylated and partially glycosylated HERV-Wenv uncleaved proteins. Beyond MSRVenv DNA copy numbers were more abundant in MS patients than in healthy humans, while syncytin-1 were unchanged. These findings reinforce the link between MSRV and MS.

Published
2009

50. Family-based transmission analysis of HLA genetic markers in Sardinian children with autistic spectrum disorders

Author

Milena Zanzottera, Salvatorica Manca, Franca Rosa Guerini, Mario Clerici, Sonia Usai, Cristina Agliardi, Stefano Sotgiu, and Elisabetta Bolognesi

Subjects
Genetic Markers, Male, Genotype, Ubiquitin-Protein Ligases, Immunology, Single-nucleotide polymorphism, Human leukocyte antigen, Biology, Polymorphism, Single Nucleotide, Linkage Disequilibrium, HLA Antigens, mental disorders, Humans, Immunology and Allergy, SNP, Family, Genetic Predisposition to Disease, Autistic Disorder, Allele, Child, Hemochromatosis Protein, Promoter Regions, Genetic, Genetics, Tumor Necrosis Factor-alpha, Histocompatibility Testing, Histocompatibility Antigens Class I, Haplotype, Membrane Proteins, General Medicine, Transmission disequilibrium test, Pedigree, Myelin-Associated Glycoprotein, Italy, Genetic marker, Child, Preschool, Microsatellite, Female, Myelin-Oligodendrocyte Glycoprotein, Myelin Proteins, Microsatellite Repeats
Abstract

Analyses of a 6-Mb region spanning the human leukocyte antigen (HLA) region from the HLA-DR to the HFE gene were performed in 37 families of Sardinian ancestry, all of whom had at least one autistic child, to identify genetic markers associated with autism spectrum disorders (ASD) development. In particular, four microsatellites (MIB, D6S265, MOGc, and D6S2239) and three single-nucleotide polymorphisms (SNPs; two in positions -308 and -238 in the promoter of the TNF-alpha and SNP rs2857766 [V142L] in exon 3 of the MOG gene) were analyzed. An intrafamilial case-control method (affected family-based controls) and transmission disequilibrium test analysis were used to evaluate the association of microsatellite and SNP markers with ASD-affected children. Results indicated positive associations with ASD for D6S265*220 (p0.01) and MOGc*131 (p0.05) and negative associations for MOGc*117 and MIB*346 alleles (p0.01) in ASD children. Polymorphism haplotype analysis indicated that D6S265 allele *220 and MOGc allele *131 were significantly more likely to be transmitted together, as a whole haplotype, to ASD children (p0.05). Conversely, the D6S265*224-MOGc*117-rs2857766(G) haplotype was significantly less frequently transmitted to ASD children (p0.01). The results present novel gene markers, reinforcing the hypothesis that genetic factors play a pivotal role in the pathogenesis of ASD.

Published
2009

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