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1. Breath-hold BOLD fMRI without CO2 sampling enables estimation of venous cerebral blood volume: potential use in normalization of stimulus-evoked BOLD fMRI data

Author

Emma Biondetti, Antonio Maria Chiarelli, Michael Germuska, Ilona Lipp, Alessandro Villani, Alessandra S. Caporale, Eleonora Patitucci, Kevin Murphy, Valentina Tomassini, and Richard G. Wise

Subjects
BOLD, fMRI, CVR, CBF, breath-hold, CBV, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

BOLD fMRI signal has been used in conjunction with vasodilatory stimulation as a marker of cerebrovascular reactivity (CVR): the relative change in cerebral blood flow (CBF) arising from a unit change in the vasodilatory stimulus. Using numerical simulations, we demonstrate that the variability in the relative BOLD signal change induced by vasodilation is strongly influenced by the variability in deoxyhemoglobin-containing cerebral blood volume (CBV), as this source of variability is likely to be more prominent than that of CVR. It may, therefore, be more appropriate to describe the relative BOLD signal change induced by an isometabolic vasodilation as a proxy of deoxygenated CBV (CBVdHb) rather than CVR. With this in mind, a new method was implemented to map a marker of CBVdHb, termed BOLD-CBV, based on the normalization of voxel-wise BOLD signal variation by an estimate of the intravascular venous BOLD signal from voxels filled with venous blood. The intravascular venous BOLD signal variation, recorded during repeated breath-holding, was extracted from the superior sagittal sinus in a cohort of 27 healthy volunteers and used as a regressor across the whole brain, yielding maps of BOLD-CBV. In the same cohort, we demonstrated the potential use of BOLD-CBV for the normalization of stimulus-evoked BOLD fMRI by comparing group-level BOLD fMRI responses to a visuomotor learning task with and without the inclusion of voxel-wise vascular covariates of BOLD-CBV and the BOLD signal change per mmHg variation in end-tidal carbon dioxide (BOLD-CVR). The empirical measure of BOLD-CBV accounted for more between-subject variability in the motor task-induced BOLD responses than BOLD-CVR estimated from end-tidal carbon dioxide recordings. The new method can potentially increase the power of group fMRI studies by including a measure of vascular characteristics and has the strong practical advantage of not requiring experimental measurement of end-tidal carbon dioxide, unlike traditional methods to estimate BOLD-CVR. It also more closely represents a specific physiological characteristic of brain vasculature than BOLD-CVR, namely blood volume.

Published
2024
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2. Changes in brain perfusion with training-related visuomotor improvement in MS

Author

Eleonora Patitucci, Ilona Lipp, Rachael Cecilia Stickland, Richard G. Wise, and Valentina Tomassini

Subjects
multiple sclerosis, MRI, perfusion, training, plasticity, recovery, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. A better understanding of the mechanisms supporting brain plasticity in MS would help to develop targeted interventions to promote recovery. A total of 29 MS patients and 19 healthy volunteers underwent clinical assessment and multi-modal MRI acquisition [fMRI during serial reaction time task (SRT), DWI, T1w structural scans and ASL of resting perfusion] at baseline and after 4-weeks of SRT training. Reduction of functional hyperactivation was observed in MS patients following the training, shown by the stronger reduction of the BOLD response during task execution compared to healthy volunteers. The functional reorganization was accompanied by a positive correlation between improvements in task accuracy and the change in resting perfusion after 4 weeks’ training in right angular and supramarginal gyri in MS patients. No longitudinal changes in WM and GM measures and no correlation between task performance improvements and brain structure were observed in MS patients. Our results highlight a potential role for CBF as an early marker of plasticity, in terms of functional (cortical reorganization) and behavioral (performance improvement) changes in MS patients that may help to guide future interventions that exploit preserved plasticity mechanisms.

Published
2023
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3. Cerebrovascular reactivity in multiple sclerosis is restored with reduced inflammation during immunomodulation

Author

Antonio Maria Chiarelli, Alessandro Villani, Daniele Mascali, Nikolaos Petsas, Emma Biondetti, Alessandra Caporale, Anna Digiovanni, Eleonora Agata Grasso, Paola Ajdinaj, Maria D’Apolito, Marianna Gabriella Rispoli, Stefano Sensi, Kevin Murphy, Carlo Pozzilli, Richard G. Wise, and Valentina Tomassini

Subjects
Medicine, Science
Abstract

Abstract Cerebrovascular reactivity (CVR) reflects the capacity of the brain’s vasculature to increase blood flow following a vasodilatory stimulus. Reactivity is an essential property of the brain’s blood vessels that maintains nutrient supplies in the face of changing demand. In Multiple Sclerosis (MS), CVR may be diminished with brain inflammation and this may contribute to neurodegeneration. We test the hypothesis that CVR is altered with MS neuroinflammation and that it is restored when inflammation is reduced. Using a breath-hold task during functional Magnetic Resonance Imaging (MRI), we mapped grey matter and white matter CVRs (CVRGM and CVRWM, respectively) in 23 young MS patients, eligible for disease modifying therapy, before and during Interferon beta treatment. Inflammatory activity was inferred from the presence of Gadolinium enhancing lesions at MRI. Eighteen age and gender-matched healthy controls (HC) were also assessed. Enhancing lesions were observed in 12 patients at the start of the study and in 3 patients during treatment. Patients had lower pre-treatment CVRGM (p = 0.04) and CVRWM (p = 0.02) compared to HC. In patients, a lower pre-treatment CVRGM was associated with a lower GM volume (r = 0.60, p = 0.003). On-treatment, there was an increase in CVRGM (p = 0.02) and CVRWM (p = 0.03) that negatively correlated with pre-treatment CVR (GM: r = − 0.58, p = 0.005; WM: r = − 0.60, p = 0.003). CVR increased when enhancing lesions reduced in number (GM: r = − 0.48, p = 0.02, WM: r = − 0.62, p = 0.003). Resolution of inflammation may restore altered cerebrovascular function limiting neurodegeneration in MS. Imaging of cerebrovascular function may thereby inform tissue physiology and improve treatment monitoring.

Published
2022
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4. A tractometry principal component analysis of white matter tract network structure and relationships with cognitive function in relapsing-remitting multiple sclerosis

Author

Danka Jandric, Geoff J.M. Parker, Hamied Haroon, Valentina Tomassini, Nils Muhlert, and Ilona Lipp

Subjects
Multiple sclerosis, Cognitive impairment, MRI, Tractometry, Brain connectivity, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract

Understanding the brain changes underlying cognitive dysfunction is a key priority in multiple sclerosis (MS) to improve monitoring and treatment of this debilitating symptom. Functional connectivity network changes are associated with cognitive dysfunction, but it is less well understood how changes in normal appearing white matter relate to cognitive symptoms. If white matter tracts have network structure it would be expected that tracts within a network share susceptibility to MS pathology. In the present study, we used a tractometry approach to explore patterns of variance in white matter metrics across white matter (WM) tracts, and assessed how such patterns relate to neuropsychological test performance across cognitive domains. A sample of 102 relapsing-remitting MS patients and 27 healthy controls underwent MRI and neuropsychological testing. Tractography was performed on diffusion MRI data to extract 40 WM tracts and microstructural measures were extracted from each tract. Principal component analysis (PCA) was used to decompose metrics from all tracts to assess the presence of any co-variance structure among the tracts. Similarly, PCA was applied to cognitive test scores to identify the main cognitive domains. Finally, we assessed the ability of tract co-variance patterns to predict test performance across cognitive domains. We found that a single co-variance pattern which captured microstructure across all tracts explained the most variance (65% variance explained) and that there was little evidence for separate, smaller network patterns of pathology. Variance in this pattern was explained by effects related to lesions, but one main co-variance pattern persisted after this effect was regressed out. This main WM tract co-variance pattern contributed to explaining a modest degree of variance in one of our four cognitive domains in MS. These findings highlight the need to investigate the relationship between the normal appearing white matter and cognitive impairment further and on a more granular level, to improve the understanding of the network structure of the brain in MS.

Published
2022
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5. Case Report: Multiple Sclerosis Relapses After Vaccination Against SARS-CoV2: A Series of Clinical Cases

Author

Riccardo Nistri, Elena Barbuti, Virginia Rinaldi, Laura Tufano, Valeria Pozzilli, Antonio Ianniello, Fabiana Marinelli, Giovanna De Luca, Luca Prosperini, Valentina Tomassini, and Carlo Pozzilli

Subjects
SARS-CoV2 infection, COVID-19 vaccine, multiple sclerosis relapse, MRI activity, lesions, adverse event, Neurology. Diseases of the nervous system, RC346-429
Abstract

Objective: To describe a temporal association between COVID-19 vaccine administration and multiple sclerosis (MS) relapses.Methods: This case series study was collected in four MS Centres in Central Italy, using data from 16 MS patients who received COVID-19 vaccination and presented both clinically and radiologically confirmed relapses between March and June 2021. We collected patients' relevant medical history, including demographics, MS clinical course, disease-modifying treatment (DMT) received (if applicable), and data from MRI scans obtained after the COVID-19 vaccination.Results: Three out of 16 patients received a diagnosis of MS with a first episode occurring after COVID-19 vaccination; 13 had already a diagnosis of MS and, among them, 9 were on treatment with DMTs. Ten patients received BNT162b2/Pfizer-BioNTech, 2 patients mRNA-1273/Moderna, and 4 patients ChAdOx1 nCoV-19/AstraZeneca. All MS relapses occurred from 3 days to 3 weeks after receiving the first dose of the COVID-19 vaccination or the booster. All patients had evidence of radiological activity on MRI.Discussion: Clinical and radiological findings in these cohort of MS patients confirmed disease re/activation and suggested a temporal association between disease activity and COVID-19 vaccination. The nature of this temporal association, whether causative or incidental, remains to be established.

Published
2021
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6. Corrigendum: A Frequency-Domain Machine Learning Method for Dual-Calibrated fMRI Mapping of Oxygen Extraction Fraction (OEF) and Cerebral Metabolic Rate of Oxygen Consumption (CMRO2)

Author

Michael Germuska, Hannah Louise Chandler, Thomas Okell, Fabrizio Fasano, Valentina Tomassini, Kevin Murphy, and Richard G. Wise

Subjects
calibrated-fMRI, oxygen extraction fraction, CMRO2, OEF, machine learning, Electronic computers. Computer science, QA75.5-76.95
Published
2021
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7. Cerebral Metabolic Changes During Visuomotor Adaptation Assessed Using Quantitative fMRI

Author

Catherine Foster, Jessica J. Steventon, Daniel Helme, Valentina Tomassini, and Richard G. Wise

Subjects
calibrated fMRI, cerebral blood flow, functional MRI, motor adaptation, oxygen metabolism, Physiology, QP1-981
Abstract

The brain retains a lifelong ability to adapt through learning and in response to injury or disease-related damage, a process known as functional neuroplasticity. The neural energetics underlying functional brain plasticity have not been thoroughly investigated experimentally in the healthy human brain. A better understanding of the blood flow and metabolic changes that accompany motor skill acquisition, and which facilitate plasticity, is needed before subsequent translation to treatment interventions for recovery of function in disease. The aim of the current study was to characterize cerebral blood flow (CBF) and oxygen consumption (relative CMRO2) responses, using calibrated fMRI conducted in 20 healthy participants, during performance of a serial reaction time task which induces rapid motor adaptation. Regions of interest (ROIs) were defined from areas showing task-induced BOLD and CBF responses that decreased over time. BOLD, CBF and relative CMRO2 responses were calculated for each block of the task. Motor and somatosensory cortices and the cerebellum showed statistically significant positive responses to the task compared to baseline, but with decreasing amplitudes of BOLD, CBF, and CMRO2 response as the task progressed. In the cerebellum, there was a sustained positive BOLD response in the absence of a significant CMRO2 increase from baseline, for all but the first task blocks. This suggests that the brain may continue to elevate the supply energy even after CMRO2 has returned to near baseline levels. Relying on BOLD fMRI data alone in studies of plasticity may not reveal the nature of underlying metabolic responses and their changes over time. Calibrated fMRI approaches may offer a more complete picture of the energetic changes supporting plasticity and learning.

Published
2020
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8. Assessment of the Effects of Aerobic Fitness on Cerebrovascular Function in Young Adults Using Multiple Inversion Time Arterial Spin Labeling MRI

Author

Catherine Foster, Jessica J. Steventon, Daniel Helme, Valentina Tomassini, and Richard G. Wise

Subjects
arterial spin labeling, cerebral blood flow, cerebral hemodynamics, cerebrovascular reactivity, exercise, Physiology, QP1-981
Abstract

This cross-sectional study investigated the effects of aerobic fitness on cerebrovascular function in the healthy brain. Gray matter cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) were quantified in a sample of young adults within a normal fitness range. Based on existing Transcranial Doppler ultrasound and fMRI evidence, we predicted a positive relationship between fitness and resting gray matter CBF and CVR. Exploratory hypotheses that higher V.O2peak would be associated with higher GM volume and cognitive performance were also investigated. 20 adults underwent a V.O2peak test and a battery of cognitive tests. All subjects also underwent an MRI scan where multiple inversion time (MTI) pulsed arterial spin labeling (PASL) was used to quantify resting CBF and CVR to 5% CO2. Region of interest analysis showed a non-significant inverse correlation between whole-brain gray matter CBF and V.O2peak; r = −0.4, p = 0.08, corrected p (p′) = 0.16 and a significant positive correlation between V.O2peak and whole-brain averaged gray matter CVR; r = 0.62, p = 0.003, p′ = 0.006. Voxel-wise analysis revealed a significant inverse association between V.O2peak and resting CBF in the left and right thalamus, brainstem, right lateral occipital cortex, left intra-calcarine cortex and cerebellum. The results of this study suggest that aerobic fitness is associated with lower baseline CBF and greater CVR in young adults.

Published
2020
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9. Tractography in the presence of multiple sclerosis lesions

Author

Ilona Lipp, Greg D. Parker, Emma C. Tallantyre, Alex Goodall, Steluta Grama, Eleonora Patitucci, Phoebe Heveron, Valentina Tomassini, and Derek K. Jones

Subjects
Tractography, Diffusion tensor imaging, Spherical harmonic deconvolution, Multiple sclerosis lesions, Brain MRI, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Accurate anatomical localisation of specific white matter tracts and the quantification of their tract-specific microstructural damage in conditions such as multiple sclerosis (MS) can contribute to a better understanding of symptomatology, disease evolution and intervention effects. Diffusion MRI-based tractography is being used increasingly to segment white matter tracts as regions-of-interest for subsequent quantitative analysis. Since MS lesions can interrupt the tractography algorithm’s tract reconstruction, clinical studies frequently resort to atlas-based approaches, which are convenient but ignorant to individual variability in tract size and shape. Here, we revisit the problem of individual tractography in MS, comparing tractography algorithms using: (i) The diffusion tensor framework; (ii) constrained spherical deconvolution (CSD); and (iii) damped Richardson-Lucy (dRL) deconvolution. Firstly, using simulated and in vivo data from 29 MS patients and 19 healthy controls, we show that the three tracking algorithms respond differentially to MS pathology. While the tensor-based approach is unable to deal with crossing fibres, CSD produces spurious streamlines, in particular in tissue with high fibre loss and low diffusion anisotropy. With dRL, streamlines are increasingly interrupted in pathological tissue. Secondly, we demonstrate that despite the effects of lesions on the fibre orientation reconstruction algorithms, fibre tracking algorithms are still able to segment tracts that pass through areas with a high prevalence of lesions. Combining dRL-based tractography with an automated tract segmentation tool on data from 131 MS patients, the cortico-spinal tracts and arcuate fasciculi could be reconstructed in more than 90% of individuals. Comparing tract-specific microstructural parameters (fractional anisotropy, radial diffusivity and magnetisation transfer ratio) in individually segmented tracts to those from a tract probability map, we show that there is no systematic disease-related bias in the individually reconstructed tracts, suggesting that lesions and otherwise damaged parts are not systematically omitted during tractography. Thirdly, we demonstrate modest anatomical correspondence between the individual and tract probability-based approach, with a spatial overlap between 35 and 55%. Correlations between tract-averaged microstructural parameters in individually segmented tracts and the probability-map approach ranged between r=.53 (p

Published
2020
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10. A Frequency-Domain Machine Learning Method for Dual-Calibrated fMRI Mapping of Oxygen Extraction Fraction (OEF) and Cerebral Metabolic Rate of Oxygen Consumption (CMRO2)

Author

Michael Germuska, Hannah Louise Chandler, Thomas Okell, Fabrizio Fasano, Valentina Tomassini, Kevin Murphy, and Richard G. Wise

Subjects
calibrated-fMRI, oxygen extraction fraction, CMRO2, OEF, machine learning, Electronic computers. Computer science, QA75.5-76.95
Abstract

Magnetic resonance imaging (MRI) offers the possibility to non-invasively map the brain's metabolic oxygen consumption (CMRO2), which is essential for understanding and monitoring neural function in both health and disease. However, in depth study of oxygen metabolism with MRI has so far been hindered by the lack of robust methods. One MRI method of mapping CMRO2 is based on the simultaneous acquisition of cerebral blood flow (CBF) and blood oxygen level dependent (BOLD) weighted images during respiratory modulation of both oxygen and carbon dioxide. Although this dual-calibrated methodology has shown promise in the research setting, current analysis methods are unstable in the presence of noise and/or are computationally demanding. In this paper, we present a machine learning implementation for the multi-parametric assessment of dual-calibrated fMRI data. The proposed method aims to address the issues of stability, accuracy, and computational overhead, removing significant barriers to the investigation of oxygen metabolism with MRI. The method utilizes a time-frequency transformation of the acquired perfusion and BOLD-weighted data, from which appropriate feature vectors are selected for training of machine learning regressors. The implemented machine learning methods are chosen for their robustness to noise and their ability to map complex non-linear relationships (such as those that exist between BOLD signal weighting and blood oxygenation). An extremely randomized trees (ET) regressor is used to estimate resting blood flow and a multi-layer perceptron (MLP) is used to estimate CMRO2 and the oxygen extraction fraction (OEF). Synthetic data with additive noise are used to train the regressors, with data simulated to cover a wide range of physiologically plausible parameters. The performance of the implemented analysis method is compared to published methods both in simulation and with in-vivo data (n = 30). The proposed method is demonstrated to significantly reduce computation time, error, and proportional bias in both CMRO2 and OEF estimates. The introduction of the proposed analysis pipeline has the potential to not only increase the detectability of metabolic difference between groups of subjects, but may also allow for single subject examinations within a clinical context.

Published
2020
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11. Contribution of Metabolomics to Multiple Sclerosis Diagnosis, Prognosis and Treatment

Author

Marianna Gabriella Rispoli, Silvia Valentinuzzi, Giovanna De Luca, Piero Del Boccio, Luca Federici, Maria Di Ioia, Anna Digiovanni, Eleonora Agata Grasso, Valeria Pozzilli, Alessandro Villani, Antonio Maria Chiarelli, Marco Onofrj, Richard G. Wise, Damiana Pieragostino, and Valentina Tomassini

Subjects
metabolomics, multiple sclerosis, biomarkers, disease modifying treatment, MRI, biofluids, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Metabolomics-based technologies map in vivo biochemical changes that may be used as early indicators of pathological abnormalities prior to the development of clinical symptoms in neurological conditions. Metabolomics may also reveal biochemical pathways implicated in tissue dysfunction and damage and thus assist in the development of novel targeted therapeutics for neuroinflammation and neurodegeneration. Metabolomics holds promise as a non-invasive, high-throughput and cost-effective tool for early diagnosis, follow-up and monitoring of treatment response in multiple sclerosis (MS), in combination with clinical and imaging measures. In this review, we offer evidence in support of the potential of metabolomics as a biomarker and drug discovery tool in MS. We also use pathway analysis of metabolites that are described as potential biomarkers in the literature of MS biofluids to identify the most promising molecules and upstream regulators, and show novel, still unexplored metabolic pathways, whose investigation may open novel avenues of research.

Published
2021
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12. Evidence of impaired brain activity balance after passive sensorimotor stimulation in multiple sclerosis.

Author

Nikolaos Petsas, Emanuele Tinelli, Delia Lenzi, Valentina Tomassini, Emilia Sbardella, Francesca Tona, Eytan Raz, Valter Nucciarelli, Carlo Pozzilli, and Patrizia Pantano

Subjects
Medicine, Science
Abstract

OBJECTIVES: Examination of sensorimotor activation alone in multiple sclerosis (MS) patients may not yield a comprehensive view of cerebral response to task stimulation. Additional information may be obtained by examining the negative BOLD response (deactivation). Aim of this work was to characterize activation and deactivation patterns during passive hand movements in MS patients. METHODS: 13 relapsing remitting-MS patients (RRMS), 18 secondary progressive-MS patients (SPMS) and 15 healthy controls (HC) underwent an fMRI study during passive right-hand movements. Activation and deactivation contrasts in the three groups were entered into ANOVA, age and gender corrected. Post-hoc analysis was performed with one-sample and two-sample t-tests. For each patient we obtained lesion volume (LV) from both T1- and T2-weighted images. RESULTS: Activations showed a progressive extension to the ipsilateral brain hemisphere according to the group and the clinical form (HC

Published
2013
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13. 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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18. Pathophysiology of <scp>MS</scp> damage and repair: linking cerebral hypoperfusion to the development of irreversible tissue loss in <scp>MS</scp> using <scp>MRI</scp>

Author

Daniele Mascali, Alessandro Villani, Antonio M. Chiarelli, Emma Biondetti, Ilona Lipp, Anna Digiovanni, Valeria Pozzilli, Alessandra S. Caporale, Marianna G. Rispoli, Paola Ajdinaj, Maria D’Apolito, Eleonora Grasso, Stefano L. Sensi, Kevin Murphy, Valentina Tomassini, and Richard G. Wise

Subjects
Neurology, Neurology (clinical)
Published
2023

19. 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

21. A flow-diffusion model of oxygen transport for quantitative mapping of cerebral metabolic rate of oxygen (CMRO

Author

Antonio M, Chiarelli, Michael, Germuska, Hannah, Chandler, Rachael, Stickland, Eleonora, Patitucci, Emma, Biondetti, Daniele, Mascali, Neeraj, Saxena, Sharmila, Khot, Jessica, Steventon, Catherine, Foster, Ana E, Rodríguez-Soto, Erin, Englund, Kevin, Murphy, Valentina, Tomassini, Felix W, Wehrli, and Richard G, Wise

Subjects
Hypercapnia, Oxygen, Oxygen Consumption, Cerebrovascular Circulation, Brain, Humans, Original Articles, Carbon Dioxide, Magnetic Resonance Imaging
Abstract

One promising approach for mapping CMRO(2) is dual-calibrated functional MRI (dc-fMRI). This method exploits the Fick Principle to combine estimates of CBF from ASL, and OEF derived from BOLD-ASL measurements during arterial O(2) and CO(2) modulations. Multiple gas modulations are required to decouple OEF and deoxyhemoglobin-sensitive blood volume. We propose an alternative single gas calibrated fMRI framework, integrating a model of oxygen transport, that links blood volume and CBF to OEF and creates a mapping between the maximum BOLD signal, CBF and OEF (and CMRO(2)). Simulations demonstrated the method’s viability within physiological ranges of mitochondrial oxygen pressure, P(m)O(2), and mean capillary transit time. A dc-fMRI experiment, performed on 20 healthy subjects using O(2) and CO(2) challenges, was used to validate the approach. The validation conveyed expected estimates of model parameters (e.g., low P(m)O(2)), with spatially uniform OEF maps (grey matter, GM, OEF spatial standard deviation ≈ 0.13). GM OEF estimates obtained with hypercapnia calibrated fMRI correlated with dc-fMRI (r = 0.65, p = 2·10(−3)). For 12 subjects, OEF measured with dc-fMRI and the single gas calibration method were correlated with whole-brain OEF derived from phase measures in the superior sagittal sinus (r = 0.58, p = 0.048; r = 0.64, p = 0.025 respectively). Simplified calibrated fMRI using hypercapnia holds promise for clinical application.

Published
2023

22. Management of hepatitis B virus prophylaxis in patients treated with disease-modifying therapies for multiple sclerosis: a multicentric Italian retrospective study

Author

Antonio Riccardo, Buonomo, Giulio, Viceconte, Massimiliano, Calabrese, Giovanna, De Luca, Valentina, Tomassini, Paola, Cavalla, Giorgia Teresa, Maniscalco, Diana, Ferraro, Viviana, Nociti, Marta, Radaelli, Maria Chiara, Buscarinu, Damiano, Paolicelli, Alberto, Gajofatto, Pietro, Annovazzi, Federica, Pinardi, Massimiliano, Di Filippo, Cinzia, Cordioli, Emanuela, Zappulo, Riccardo, Scotto, Ivan, Gentile, Antonio Luca, Spiezia, Martina, Petruzzo, Marcello, De Angelis, Vincenzo, Brescia Morra, Claudio, Solaro, Claudio, Gasperini, Eleonora, Cocco, Marcello, Moccia, Roberta, Lanzillo, Buonomo, ANTONIO RICCARDO, Viceconte, Giulio, Calabrese, Massimiliano, De Luca, Giovanna, Tomassini, Valentina, Cavalla, Paola, Maniscalco Giorgia, Teresa, Ferraro, Diana, Nociti, Viviana, Radaelli, Marta, Buscarinu Maria, Chiara, Paolicelli, Damiano, Gajofatto, Alberto, Annovazzi, Pietro, Pinardi, Federica, Di Filippo, Massimiliano, Cordioli, Cinzia, Zappulo, Emanuela, Scotto, Riccardo, Gentile, Ivan, Spiezia, Antonio, Petruzzo, Martina, DE ANGELIS, Marcello, BRESCIA MORRA, Vincenzo, Solaro, Claudio, Gasperini, Claudio, Cocco, Eleonora, Moccia, Marcello, and Lanzillo, Roberta

Subjects
Hepatitis B virus, Multiple Sclerosis, Vaccination, Middle Aged, Hepatitis B, Antiviral Agents, Neurology, DNA, Viral, Cladribine, Humans, Virus Activation, Ocrelizumab, Neurology (clinical), Rituximab, Retrospective Studies
Abstract

Background Patients with multiple sclerosis (MS) often receive disease-modifying therapies (DMTs) that can expose them to reactivation of potential occult hepatitis B virus (HBV) infection (pOBI). We aimed to evaluate the MS Centers behavior regarding HBV screening and prophylaxis in a large cohort of MS patients receiving anti-CD20 or cladribine. Methods Retrospective, multicentric study recruiting Italian MS patients treated with rituximab, ocrelizumab and cladribine. Results We included 931 MS patients from 15 centers. All but 38 patients performed a complete HBV screening. Patients’ age > 50 years was significantly associated with no history of vaccination and HBsAb titres p p = 0.5), pre-or post-therapy vaccination (p = 0.2) and number of previous DMTs (p = 0.2). Among pOBI patients (n = 53), 21 received antiviral prophylaxis, while only 13 had HBV DNA monitoring and 19 patients neither monitored HBV DNA nor received prophylaxis. Conclusions Baseline HBV screening in patients receiving anti-CD20 and cladribine is a consolidated practice. Nonetheless, HBV vaccination coverage is still lacking in such population and age is a significant factor associated with low HBV protection. Rituximab, ocrelizumab and cladribine did not impair HBV vaccine response. Almost 35% of pOBI patients fail to receive HBVr prevention. Management of HBV prophylaxis could be improved in MS patients and further prospective studies are needed to assess the effectiveness of prophylactic strategies in such patients.

Published
2022

24. 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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26. Mechanisms of Network Changes in Cognitive Impairment in Multiple Sclerosis

Author

Hamied A. Haroon, Laura M. Parkes, Geoff J M Parker, G Castellazzi, Danka Jandric, Ilona Lipp, Valentina Tomassini, Nils Muhlert, David Rog, and David Paling

Subjects
Brain Mapping, Multiple Sclerosis, medicine.diagnostic_test, business.industry, Multiple sclerosis, Functional connectivity, Neuropsychology, Brain, Magnetic resonance imaging, Neuropsychological Tests, medicine.disease, Magnetic Resonance Imaging, Cross-Sectional Studies, Cerebral blood flow, Fractional anisotropy, Humans, Medicine, Cognitive Dysfunction, Neurology (clinical), business, Cognitive impairment, Neuroscience, Default mode network
Abstract

Background and ObjectivesCognitive impairment in multiple sclerosis (MS) is associated with functional connectivity abnormalities. While there have been calls to use functional connectivity measures as biomarkers, there remains to be a full understanding of why they are affected in MS. In this cross-sectional study, we tested the hypothesis that functional network regions may be susceptible to disease-related “wear and tear” and that this can be observable on co-occurring abnormalities on other magnetic resonance metrics. We tested whether functional connectivity abnormalities in cognitively impaired patients with MS co-occur with (1) overlapping, (2) local, or (3) distal changes in anatomic connectivity and cerebral blood flow abnormalities.MethodsMultimodal 3T MRI and assessment with the Brief Repeatable Battery of Neuropsychological tests were performed in 102 patients with relapsing-remitting MS and 27 healthy controls. Patients with MS were classified as cognitively impaired if they scored ≥1.5 SDs below the control mean on ≥2 tests (n = 55) or as cognitively preserved (n = 47). Functional connectivity was assessed with Independent Component Analysis and dual regression of resting-state fMRI images. Cerebral blood flow maps were estimated, and anatomic connectivity was assessed with anatomic connectivity mapping and fractional anisotropy of diffusion-weighted MRI. Changes in cerebral blood flow and anatomic connectivity were assessed within resting-state networks that showed functional connectivity abnormalities in cognitively impaired patients with MS.ResultsFunctional connectivity was significantly decreased in the anterior and posterior default mode networks and significantly increased in the right and left frontoparietal networks in cognitively impaired relative to cognitively preserved patients with MS (threshold-free cluster enhancement corrected at p ≤ 0.05, 2 sided). Networks showing functional abnormalities showed altered cerebral blood flow and anatomic connectivity locally and distally but not in overlapping locations.DiscussionWe provide the first evidence that functional connectivity abnormalities are accompanied by local cerebral blood flow and structural connectivity abnormalities but also demonstrate that these effects do not occur in exactly the same location. Our findings suggest a possibly shared pathologic mechanism for altered functional connectivity in brain networks in MS.

Published
2021

27. Reduced brain oxygen metabolism in patients with multiple sclerosis: Evidence from dual-calibrated functional MRI

Author

Hannah L Chandler, Rachael C Stickland, Eleonora Patitucci, Michael Germuska, Antonio M Chiarelli, Catherine Foster, Shona Bhome-Dhaliwal, Thomas M Lancaster, Neeraj Saxena, Sharmila Khot, Valentina Tomassini, and Richard G Wise

Subjects
Oxygen, Multiple Sclerosis, Neurology, Humans, Brain, Neurology (clinical), Cardiology and Cardiovascular Medicine, Magnetic Resonance Imaging
Abstract

Cerebral energy deficiency is increasingly recognised as an important feature of multiple sclerosis (MS). Until now, we have lacked non-invasive imaging methods to quantify energy utilisation and mitochondrial function in the human brain. Here, we used novel dual-calibrated functional magnetic resonance imaging (dc-fMRI) to map grey-matter (GM) deoxy-haemoglobin sensitive cerebral blood volume (CBVdHb), cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen consumption (CMRO2) in patients with MS (PwMS) and age/sex matched controls. By integrating a flow-diffusion model of oxygen transport, we evaluated the effective oxygen diffusivity of the capillary network (DC) and the partial pressure of oxygen at the mitochondria (PmO2). Significant between-group differences were observed as decreased CBF ( p = 0.010), CMRO2 ( p C ( p = 0.002), and increased PmO2 ( p = 0.043) in patients compared to controls. No significant differences were observed for CBVdHb ( p = 0.389), OEF ( p = 0.358), or GM volume ( p = 0.302). Regional analysis showed widespread reductions in CMRO2 and DC for PwMS. Our findings may be indicative of reduced oxygen demand or utilisation in the MS brain and mitochondrial dysfunction. Our results suggest changes in brain physiology may precede MRI-detectable GM loss and may contribute to disease progression and neurodegeneration.

Published
2022

28. Contemporary study of multiple sclerosis disability in South East Wales

Author

Katharine Elizabeth Harding, Gillian Ingram, Emma Clare Tallantyre, Fady Joseph, Mark Wardle, Trevor P Pickersgill, Mark D Willis, Valentina Tomassini, Owen Rhys Pearson, and Neil P Robertson

Subjects
Psychiatry and Mental health, Surgery, Neurology (clinical)
Abstract

BackgroundA contemporary understanding of disability evolution in multiple sclerosis (MS) is an essential tool for individual disease management and planning of interventional studies. We have used prospectively collected longitudinal data to analyse disability progression and variation in a British MS cohort.MethodsCox proportional hazards regression was used to estimate hazard of Expanded Disability Status Scale (EDSS) 4.0 and 6.0. A continuous Markov model was used to estimate transitional probabilities for individual EDSS scores. Models were adjusted for age at MS onset, sex and disease-modifying treatments (DMTs) exposure.Results2135 patients were included (1487 (70%) female, 1922 (89%) relapsing onset). 865 (41%) had used DMTs. Median time to EDSS 4.0 and 6.0 was 18.2 years (95% CI 16.3 to 20.2) and 22.1 years (95% CI 20.5 to 24.5). In the Markov model, the median time spent at EDSS scores of ConclusionsThese data provide a detailed contemporary model of disability outcomes in a representative population-based MS cohort. They support a trend of increasing time to disability milestones compared with historical reference populations, and document disability variation with the use of transitional matrices. In addition, they provide essential information for patient counselling, clinical trial design, service planning and offer a comparative baseline for assessment of therapeutic interventions.

Published
2022

29. Double courage, women as translation pioneers

Author

Valentina Tomassini

Subjects
Estudios de traducción, Género y traducción, Canadian feminist translation, Translatresses, Management of Technology and Innovation, Traductoras, Traducción feminista canadiense, Gender and translation, Translation studies
Abstract

En muchas teorías traductológicas se ha evidenciado un paralelismo entre el estatus del texto traducido, considerado inferior a la obra original, y el de las mujeres, subestimadas tanto en la sociedad como en la literatura. Por lo tanto, en las últimas décadas, la perspectiva de género se ha ocupado de rescatar el trabajo de las traductoras y de de-construir una teoría que no había incorporado a las mujeres en el proceso de estudio del fenómeno y en la reflexión crítica. En concreto, en este artículo pretendemos dar una muestra de la innovación que las mujeres han aportado en este campo y de las estrategias que han llevado a cabo para subrayar su identidad en el texto. Debido a la centralidad del mundo anglonorteamericano en las especulaciones de género sobre traducción, nuestro recorrido se fundamenta sobre todo en el trabajo de las investigadoras y traductoras canadienses, para luego abrirse a un breve estado de la cuestión acerca de la recepción que su pensamiento ha tenido en el contexto español. Many translation theories pointed out a similarity between the status of the translated text, which was considered as inferior to the original, and the women’s one, because of their underestimation both in society and literature. For this reason, during the last decades, gender perspective has tried to recover translatress’works and to deconstruct a theory that hadn’t involved women in its studies on the translation process. In particular, in this article we would like to show women’s innovation in this field and the strategies they have created to underline their identity in the text. Because of the importance of Anglo-American theories about gender and translation, our work is primarily based on feminist translation school in Canada, in order to analyse, then, its reception in the Spanish context.

Published
2021

30. A flow-diffusion model of oxygen transport for quantitative mapping of cerebral metabolic rate of oxygen (CMRO2) with single gas calibrated fMRI

Author

Antonio M Chiarelli, Michael Germuska, Hannah Chandler, Rachael Stickland, Eleonora Patitucci, Emma Biondetti, Daniele Mascali, Neeraj Saxena, Sharmila Khot, Jessica Steventon, Catherine Foster, Ana E Rodríguez-Soto, Erin Englund, Kevin Murphy, Valentina Tomassini, Felix W Wehrli, and Richard G Wise

Subjects
Neurology, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

One promising approach for mapping CMRO2 is dual-calibrated functional MRI (dc-fMRI). This method exploits the Fick Principle to combine estimates of CBF from ASL, and OEF derived from BOLD-ASL measurements during arterial O2 and CO2 modulations. Multiple gas modulations are required to decouple OEF and deoxyhemoglobin-sensitive blood volume. We propose an alternative single gas calibrated fMRI framework, integrating a model of oxygen transport, that links blood volume and CBF to OEF and creates a mapping between the maximum BOLD signal, CBF and OEF (and CMRO2). Simulations demonstrated the method’s viability within physiological ranges of mitochondrial oxygen pressure, PmO2, and mean capillary transit time. A dc-fMRI experiment, performed on 20 healthy subjects using O2 and CO2 challenges, was used to validate the approach. The validation conveyed expected estimates of model parameters (e.g., low PmO2), with spatially uniform OEF maps (grey matter, GM, OEF spatial standard deviation ≈ 0.13). GM OEF estimates obtained with hypercapnia calibrated fMRI correlated with dc-fMRI (r = 0.65, p = 2·10−3). For 12 subjects, OEF measured with dc-fMRI and the single gas calibration method were correlated with whole-brain OEF derived from phase measures in the superior sagittal sinus (r = 0.58, p = 0.048; r = 0.64, p = 0.025 respectively). Simplified calibrated fMRI using hypercapnia holds promise for clinical application.

Published
2022

32. 'Better explanations' in multiple sclerosis diagnostic workup

Author

Massimiliano Calabrese 1, Claudio Gasperini 2, Carla Tortorella 2, Gianmarco Schiavi 2, Giovanni Frisullo 2, Paolo Ragonese, Roberta Fantozzi 2, Luca Prosperini 2, Pietro Annovazzi 2, Cinzia Cordioli 2, Massimiliano Di Filippo 2, Diana Ferraro 2, Alberto Gajofatto 2, Simona Malucchi 2, Salvatore Lo Fermo 2, Giovanna De Luca 2, Maria L Stromillo 2, Eleonora Cocco 2, Antonio Gallo 2, Damiano Paolicelli 2, Roberta Lanzillo 2, Valentina Tomassini 2, Ilaria Pesci 2, Maria E Rodegher 2, Claudio Solaro 2, RIREMS group (Rising Italian Researchers in Multiple Sclerosis), Massimiliano Calabrese 1 , Claudio Gasperini 2 , Carla Tortorella 2 , Gianmarco Schiavi 2 , Giovanni Frisullo 2 , Paolo Ragonese , Roberta Fantozzi 2 , Luca Prosperini 2 , Pietro Annovazzi 2 , Cinzia Cordioli 2 , Massimiliano Di Filippo 2 , Diana Ferraro 2 , Alberto Gajofatto 2 , Simona Malucchi 2 , Salvatore Lo Fermo 2 , Giovanna De Luca 2 , Maria L Stromillo 2 , Eleonora Cocco 2 , Antonio Gallo 2 , Damiano Paolicelli 2 , Roberta Lanzillo 2 , Valentina Tomassini 2 , Ilaria Pesci 2 , Maria E Rodegher 2 , Claudio Solaro 2 , RIREMS group (Rising Italian Researchers in Multiple Sclerosis), Calabrese, M., Gasperini, C., Tortorella, C., Schiavi, G., Frisullo, G., Ragonese, P., Fantozzi, R., Prosperini, L., Annovazzi, P., Cordioli, C., Di Filippo, M., Ferraro, D., Gajofatto, A., Malucchi, S., Lo Fermo, S., De Luca, G., Stromillo, M. L., Cocco, E., Gallo, A., Paolicelli, D., Lanzillo, R., Tomassini, V., Pesci, I., Rodegher, M. E., Solaro, C., Calabrese, Massimiliano, Gasperini, Claudio, Tortorella, Carla, Schiavi, Gianmarco, Frisullo, Giovanni, Ragonese, Paolo, Fantozzi, Roberta, Prosperini, Luca, Annovazzi, Pietro, Cordioli, Cinzia, Di Filippo, Massimiliano, Ferraro, Diana, Gajofatto, Alberto, Malucchi, Simona, Lo Fermo, Salvatore, De Luca, Giovanna, Stromillo, Maria L, Cocco, Eleonora, Gallo, Antonio, Paolicelli, Damiano, Lanzillo, Roberta, Tomassini, Valentina, Pesci, Ilaria, Rodegher, Maria E, and Solaro, Claudio

Subjects
Male, Longitudinal Studie, Disease, 0302 clinical medicine, Multiple Sclerosi, Diagnosis, Medicine, 030212 general & internal medicine, Prospective Studies, Longitudinal Studies, Prospective cohort study, medicine.diagnostic_test, Magnetic Resonance Imaging, clinical practice, atypical MRI lesions, MS mimics, Disease Progression, Female, Settore MED/26 - Neurologia, Radiology, Human, Adult, multiple sclerosis, diagnostic criteria, medicine.medical_specialty, Multiple Sclerosis, omarkers / metabolism Diagnosis, Differential Female Follow-Up Studies Humans Longitudinal Studies Magnetic Resonance Imaging Male Multiple Sclerosis / diagnosis* Prospective Studies, Article, Follow-Up Studie, Diagnosis, Differential, 03 medical and health sciences, Humans, Neuromyelitis optica, business.industry, Multiple sclerosis, Biomarkers, Follow-Up Studies, Magnetic resonance imaging, Odds ratio, Biomarker, medicine.disease, Migraine, Differential, Neurology (clinical), Differential diagnosis, business, 030217 neurology & neurosurgery
Abstract

BackgroundThe exclusion of other diseases that can mimic multiple sclerosis (MS) is the cornerstone of current diagnostic criteria. However, data on the frequency of MS mimics in real life are incomplete.MethodsA total of 695 patients presenting with symptoms suggestive of MS in any of the 22 RIREMS centers underwent a detailed diagnostic workup, including a brain and spinal cord MRI scan, CSF and blood examinations, and a 3-year clinical and radiologic follow-up.FindingsA total of 667 patients completed the study. Alternative diagnoses were formulated in 163 (24.4%) cases, the most frequent being nonspecific neurologic symptoms in association with atypical MRI lesions of suspected vascular origin (40 patients), migraine with atypical lesions (24 patients), and neuromyelitis optica (14 patients). MS was diagnosed in 401 (60.1%) patients according to the 2017 diagnostic criteria. The multivariate analysis revealed that the absence of CSF oligoclonal immunoglobulin G bands (IgG-OB) (odds ratio [OR] 18.113), the presence of atypical MRI lesions (OR 10.977), the absence of dissemination in space (DIS) of the lesions (OR 5.164), and normal visual evoked potentials (OR 3.550) were all independent predictors of an alternative diagnosis.InterpretationThis observational, unsponsored, real-life study, based on clinical practice, showed that diseases that mimicked MS were many, but more than 45% were represented by nonspecific neurologic symptoms with atypical MRI lesions of suspected vascular origin, migraine, and neuromyelitis optica. The absence of IgG-OB and DIS, the presence of atypical MRI lesions, and normal visual evoked potentials should be considered suggestive of an alternative disease and red flags for the misdiagnosis of MS.

Published
2019

34. Similarities and differences between multiple sclerosis and type 1 diabetes

Author

Valeria Pozzilli, Eleonora Grasso, and Valentina Tomassini

Subjects
Type 1 diabetes, Multiple Sclerosis, business.industry, Endocrinology, Diabetes and Metabolism, Multiple sclerosis, COVID-19, medicine.disease, medicine.disease_cause, Comorbidity, Autoimmunity, Diabetes Mellitus, Type 1, Endocrinology, Immune system, Transgender hormone therapy, Diabetes mellitus, Immunology, Internal Medicine, medicine, Genetic predisposition, Humans, business, Pandemics
Abstract

Multiple sclerosis (MS) and type 1 diabetes (T1D) are chronic conditions that result from dysfunction of the immune system. Their common root in autoimmunity stimulates interest in the exploration of similarities and differences between the two diseases. Genetic susceptibility is relevant, creating a substrate, on which environmental factors act as a trigger of an aberrant immune response. Despite being both T-cell mediated disorders with a strong involvement of the humoral arm, immunomodulation is a mainstay of MS management, whereas hormone replacement therapy remains the principal approach for T1D. T1D is usually diagnosed in children and adolescents, while MS is typical of young adults. This difference has implications for disease progression and treatment. The SARS-CoV-2 pandemic and its effect on immunity may affect the prevalence of these conditions, as well as their clinical manifestation.

Published
2021

35. Contribution of Metabolomics to Multiple Sclerosis Diagnosis, Prognosis and Treatment

Author

Silvia Valentinuzzi, Giovanna De Luca, Antonio Maria Chiarelli, Valentina Tomassini, Damiana Pieragostino, Richard G. Wise, Eleonora Grasso, Piero Del Boccio, Alessandro Villani, Anna Digiovanni, Marianna Gabriella Rispoli, Luca Federici, Maria di Ioia, Valeria Pozzilli, and Marco Onofrj

Subjects
Multiple Sclerosis, QH301-705.5, biofluids, Review, Bioinformatics, Catalysis, Inorganic Chemistry, Metabolomics, Medicine, Animals, Humans, disease modifying treatment, Biology (General), Physical and Theoretical Chemistry, QD1-999, Molecular Biology, Spectroscopy, Neuroinflammation, business.industry, Drug discovery, Multiple sclerosis, Organic Chemistry, Neurodegeneration, biomarkers, General Medicine, Pathway analysis, medicine.disease, Prognosis, metabolomics, Computer Science Applications, Chemistry, Potential biomarkers, Metabolome, Biomarker (medicine), business, MRI
Abstract

Metabolomics-based technologies map in vivo biochemical changes that may be used as early indicators of pathological abnormalities prior to the development of clinical symptoms in neurological conditions. Metabolomics may also reveal biochemical pathways implicated in tissue dysfunction and damage and thus assist in the development of novel targeted therapeutics for neuroinflammation and neurodegeneration. Metabolomics holds promise as a non-invasive, high-throughput and cost-effective tool for early diagnosis, follow-up and monitoring of treatment response in multiple sclerosis (MS), in combination with clinical and imaging measures. In this review, we offer evidence in support of the potential of metabolomics as a biomarker and drug discovery tool in MS. We also use pathway analysis of metabolites that are described as potential biomarkers in the literature of MS biofluids to identify the most promising molecules and upstream regulators, and show novel, still unexplored metabolic pathways, whose investigation may open novel avenues of research.

Published
2021

36. 059 Secondary progressive MS in the UK: a prospective cohort study

Author

Katharine Harding, Fady Joseph, Trevor Pickersgill, Valentina Tomassini, Emma Tallantyre, and Neil Robertson

Subjects
Psychiatry and Mental health, Surgery, Neurology (clinical)
Abstract

BackgroundAlthough most people with relapsing onset multiple sclerosis (R-MS) eventually transition to secondary progressive multiple sclerosis (SPMS), little is known about disability progression in SPMS.MethodsAll R-MS patients in the Cardiff MS registry were included. Cox proportional hazards regression was used to examine a) hazard of converting to SPMS and b) hazard of attaining EDSS 6.0 and 8.0 in SPMS.Results1611 R-MS patients were included. Older age at MS onset (hazard ratio [HR] 1.02, 95%CI 1.01–1.03), male sex (HR 1.71, 95%CI 1.41–2.08), and residual disability after onset (HR 1.38, 95%CI 1.11–1.71) were asso- ciated with increased hazard of SPMS. Male sex (EDSS 6.0 HR 1.41 [1.04–1.90], EDSS 8.0 HR 1.75 [1.14–2.69]) and higher EDSS at SPMS onset (EDSS 6.0 HR 1.31 [1.17–1.46]; EDSS 8.0 HR 1.38 [1.19–1.61]) were associated with increased hazard of reaching disability milestones, while older age at SPMS was associated with a lower hazard of progression (EDSS 6.0 HR 0.94 [0.92–0.96]; EDSS 8.0: HR 0.92 [0.90–0.95]).ConclusionsDifferent factors are associated with hazard of SPMS compared to hazard of disability progres- sion after SPMS onset. These data may be used to plan services, and provide a baseline for comparison for future interventional studies and has relevance for new treatments for SPMSRobertsonNP@cardiff.ac.uk

Published
2022

37. Concurrent anatomical, physiological and network changes in cognitively impaired multiple sclerosis patients

Author

David Rog, Nils Muhlert, Danka Jandric, Ilona Lipp, Laura M. Parkes, Geoff J M Parker, Hamied A. Haroon, David Paling, G Castellazzi, and Valentina Tomassini

Subjects
Cerebral blood flow, Resting state fMRI, business.industry, Multiple sclerosis, Fractional anisotropy, Neuropsychology, Medicine, Cognition, business, medicine.disease, Neuroscience, Pathological, Default mode network
Abstract

Cognitive impairment in multiple sclerosis is associated with functional connectivity abnormalities, but the pathological substrates of these abnormalities are not well understood. It has been proposed that resting-state network nodes that integrate information from disparate regions are susceptible to metabolic stress, which may impact functional connectivity. In multiple sclerosis, pathology could increase metabolic stress within axons, damaging the anatomical connections of network regions, and leading to functional connectivity changes. We tested this hypothesis by assessing whether resting state network regions that show functional connectivity abnormalities in people with cognitive impairment also show anatomical connectivity abnormalities.Multimodal MRI and neuropsychological assessments were performed in 102 relapsing remitting multiple sclerosis patients and 27 healthy controls. Patients were considered cognitively impaired if they obtained a z-score of ≤1.5 on ≥2 tests of the Brief Repeatable Battery of Neuropsychological Tests (n=55). Functional connectivity was assessed with Independent Component Analysis of resting state fMRI images, and anatomical connectivity with Anatomical Connectivity Mapping of diffusion-weighted MRI. Exploratory analyses of fractional anisotropy and cerebral blood flow changes were conducted to assess local tissue characteristics.We found significantly decreased functional connectivity in the anterior and posterior default mode networks and significant increases in the right and left frontoparietal networks in cognitively impaired relative to cognitively preserved patients. Networks showing functional abnormalities also showed reduced anatomical connectivity and white matter microstructure integrity as well as reduced local tissue cerebral blood flow.Our results identify key pathological correlates of functional connectivity abnormalities associated with impaired cognitive function in multiple sclerosis, consistent with metabolic dysfunction in functional network regions.

Published
2021

38. Real world experience with teriflunomide in multiple sclerosis: the TER-Italy study

Author

Pietro Annovazzi, Fioravante Capone, Sofia Zywicki, Paola Cavalla, Claudio Gasperini, Roberta Fantozzi, Elisabetta Ferraro, Doriana Landi, Sebastiano Bucello, Maria Maddalena Filippi, Roberto Bergamaschi, Vincenzo Dattola, Luigi M.E. Grimaldi, Girolama Alessandra Marfia, Luca Prosperini, Paolo Ragonese, Paolo Manganotti, Cristina Zuliani, Marco Pisa, Maria Chiara Buscarinu, Giovanna Borriello, A. Bianchi, Massimiliano Mirabella, Antonio Cortese, Marta Altieri, Rosella Cavarretta, Valentina Liliana Adriana Torri-Clerici, Giovanna De Luca, Valentina Tomassini, Massimiliano Di Filippo, Graziella Callari, Massimo Filippi, Giulia Mallucci, Valeria Barcella, Mauro Zaffaroni, Marco Capobianco, Paola Perini, Margherita Russo, Sabrina Realmuto, Marianna Lo Re, Bucello S., Annovazzi P., Ragonese P., Altieri M., Barcella V., Bergamaschi R., Bianchi A., Borriello G., Buscarinu M.C., Callari G., Capobianco M., Capone F., Cavalla P., Cavarretta R., Cortese A., De Luca G., Di Filippo M., Dattola V., Fantozzi R., Ferraro E., Filippi M.M., Gasperini C., Grimaldi L.M.E., Landi D., Re M.L., Mallucci G., Manganotti P., Marfia G.A., Mirabella M., Perini P., Pisa M., Realmuto S., Russo M., Tomassini V., Torri-Clerici V.L.A., Zaffaroni M., Zuliani C., Zywicki S., Filippi M., and Prosperini L.

Subjects
medicine.medical_specialty, Neurology, Multiple Sclerosis, Toluidines, Hydroxybutyrates, Oral drugs, Disease, Relapsing-Remitting, Settore MED/26, Pregnancy planning, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, Teriflunomide, Nitriles, medicine, Humans, 030212 general & internal medicine, Adverse effect, Retrospective Studies, Expanded Disability Status Scale, business.industry, Multiple sclerosis, medicine.disease, Settore MED/26 - NEUROLOGIA, chemistry, Tolerability, Italy, Crotonates, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Objective: To identify baseline factors associated with disease activity in patients with relapsing–remitting multiple sclerosis (RRMS) under teriflunomide treatment. Methods: This was an independent, multi-centre, retrospective post-marketing study. We analysed data of 1,507 patients who started teriflunomide since October 2014 and were regularly followed in 28 Centres in Italy. We reported the proportions of patients who discontinued treatment (after excluding 32 lost to follow-up) and who experienced clinical disease activity, i.e., relapse(s) and/or confirmed disability worsening, as assessed by the Expanded Disability Status Scale (EDSS). Decision tree-based analysis was performed to identify baseline factors associated with clinical disease activity during teriflunomide treatment. Results: At database lock (September 2020), approximately 29% of patients (430 out of 1,475) discontinued teriflunomide because of disease activity (~ 46%), adverse events (~ 37%), poor tolerability (~ 15%), pregnancy planning (~ 2%). Approximately 28% of patients experienced disease activity over a median follow-up of 2.75years: ~ 9% had relapses but not disability worsening; ~ 13% had isolated disability worsening; ~ 6% had both relapses and disability worsening. The most important baseline factor associated with disease activity(especially disability worsening) was an EDSS > 4.0 (p < 0.001). In patients with moderate disability level (EDSS 2.0–4.0), disease activity occurred more frequently in case of ≥ 1 pre-treatment relapses (p = 0.025). In patients with milder disability level (EDSS < 2.0), disease activity occurred more frequently after previous exposure to ≥ 2 disease-modifying treatments (p = 0.007). Conclusions: Our study suggests a place-in-therapy for teriflunomide in naïve patients with mild disability level or in those who switched their initial treatment for poor tolerability. Adverse events related with teriflunomide were consistent with literature data, without any new safety concern.

Published
2021

39. Using dual-calibrated functional MRI to map brain oxygen supply and consumption in multiple sclerosis

Author

Thomas M. Lancaster, Rachael C. Stickland, Hannah L. Chandler, Neeraj Saxena, Sharmila Khot, Shona Bhome-Dhaliwal, Catherine Foster, Richard G. Wise, Valentina Tomassini, Michael Germuska, and Eleonora Patitucci

Subjects
medicine.medical_specialty, Oxygen supply, business.industry, Multiple sclerosis, Significant difference, chemistry.chemical_element, Lesion volume, Grey matter, medicine.disease, Oxygen, medicine.anatomical_structure, Cerebral blood flow, chemistry, Internal medicine, Cardiology, medicine, In patient, business
Abstract

Evidence suggests that cerebrovascular function and oxygen consumption are altered in multiple sclerosis (MS). Here, we quantified the vascular and oxygen metabolic MRI burden in patients with MS (PwMS) and assessed the relationship between these MRI measures of and metrics of damage and disability. In PwMS and in matched healthy volunteers, we applied a newly developed dual-calibrated fMRI method of acquisition and analysis to map grey matter (GM) cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen consumption (CMRO2) and effective oxygen diffusivity of the capillary network (DC). We also quantified physical and cognitive function in PwMS and controls. There was no significant difference in GM volume between 22 PwMS and 20 healthy controls (p=0.302). Significant differences in CBF (PwMS vs. controls: 44.91 ± 6.10 vs. 48.90 ± 5.87 ml/100g/min, p=0.010), CMRO2 (117.69 ± 17.31 vs. 136.49 ± 14.48 μmol/100g/min pC (2.70 ± 0.51 vs. 3.18 ± 0.41 μmol/100g/mmHg/min, p=0.002) were observed in the PwMS. No significant between-group differences were observed for OEF (PwMS vs. controls: 0.38 ± 0.09 vs. 0.39 ± 0.02, p=0.358). Regional analysis showed widespread reductions in CMRO2 and DC for PwMS compared to healthy volunteers. There was a significant correlation between physiological measures and T2 lesion volume, but no association with current clinical disability. Our findings demonstrate concurrent reductions in oxygen supply and consumption in the absence of an alteration in oxygen extraction that may be indicative of a reduced demand for oxygen (O2), an impaired transfer of O2 from capillaries to mitochondria, and/or a reduced ability to utilise O2 that is available at the mitochondria. With no between-group differences in GM volume, our results suggest that changes in brain physiology may precede MRI-detectable GM loss and thus may be one of the pathological drivers of neurodegeneration and disease progression.

Published
2021

40. Defining the course of tumefactive multiple sclerosis: A large retrospective multicentre study

Author

Lorenzo Gaetani, Doriana Landi, Diana Ferraro, Paolo Ragonese, Alberto Gajofatto, Caterina Di Carmine, Paola Cavalla, Maria Pia Amato, Eleonora Cocco, Roberta Lanzillo, Alessia Manni, Roberta Fantozzi, Claudio Gasperini, D. Farina, Giuseppe Fenu, Sara Zagaglia, Raffaella Cerqua, Claudio Solaro, Antonio Gallo, Carolina Gabri Nicoletti, Pietro Iaffaldano, Federica Pinardi, Valentina Torri Clerici, Isabella Righini, Fabio Buttari, Damiano Paolicelli, Pietro Annovazzi, Carla Tortorella, Rocco Totaro, Giovanna De Luca, Chiara De Fino, Valentina Tomassini, Luca Prosperini, Marcello Moccia, Viviana Nociti, Maria Chiara Buscarinu, Maria Di Gregorio, Massimiliano Di Filippo, Di Gregorio M., Torri Clerici V.L.A., Fenu G., Gaetani L., Gallo A., Cavalla P., Ragonese P., Annovazzi P., Gajofatto A., Prosperini L., Landi D., Nicoletti C.G., Di Carmine C., Totaro R., Nociti V., De Fino C., Ferraro D., Tomassini V., Tortorella C., Righini I., Amato M.P., Manni A., Paolicelli D., Iaffaldano P., Lanzillo R., Moccia M., Buttari F., Fantozzi R., Cerqua R., Zagaglia S., Farina D., De Luca G., Buscarinu M.C., Pinardi F., Cocco E., Gasperini C., Solaro C.M., Di Filippo M., Di Gregorio, M., Torri Clerici, V. L. A., Fenu, G., Gaetani, L., Gallo, A., Cavalla, P., Ragonese, P., Annovazzi, P., Gajofatto, A., Prosperini, L., Landi, D., Nicoletti, C. G., Di Carmine, C., Totaro, R., Nociti, V., De Fino, C., Ferraro, D., Tomassini, V., Tortorella, C., Righini, I., Amato, M. P., Manni, A., Paolicelli, D., Iaffaldano, P., Lanzillo, R., Moccia, M., Buttari, F., Fantozzi, R., Cerqua, R., Zagaglia, S., Farina, D., De Luca, G., Buscarinu, M. C., Pinardi, F., Cocco, E., Gasperini, C., Solaro, C. M., and Di Filippo, M.

Subjects
Male, tumefactive demyelinating lesions (TDLs), 0302 clinical medicine, Retrospective Studie, Interquartile range, differential diagnosis, 030212 general & internal medicine, Prospective Studies, Young adult, Prospective cohort study, Child, treatment, Tumefactive multiple sclerosi, Tumefactive demyelinating lesions, Demyelinating Disease, Middle Aged, Magnetic Resonance Imaging, Differential diagnosis, Multiple sclerosis, Tumefactive demyelinating lesions, Tumefactive multiple sclerosis, Neurology, Multiple sclerosis, Tumefactive multiple sclerosis, Female, Human, Adult, medicine.medical_specialty, Multiple Sclerosis, Adolescent, differential diagnosi, Settore MED/26, 03 medical and health sciences, Young Adult, Oligoclonal Band, Internal medicine, medicine, Humans, Multiple sclerosi, Tumefactive multiple sclerosis (TuMS), Aged, Retrospective Studies, Tumefactive demyelinating lesion, Expanded Disability Status Scale, business.industry, Oligoclonal Bands, Retrospective cohort study, Odds ratio, medicine.disease, Confidence interval, Prospective Studie, Demyelinating Diseases, prognosis, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Background and purpose: Tumefactive multiple sclerosis (TuMS) (i.e., MS onset presenting with tumefactive demyelinating lesions [TDLs]) is a diagnostic and therapeutic challenge. We performed a multicentre retrospective study to describe the clinical characteristics and the prognostic factors of TuMS. Methods: One hundred two TuMS patients were included in this retrospective study. Demographic, clinical, magnetic resonance imaging (MRI), laboratory data and treatment choices were collected. Results: TuMS was found to affect women more than men (female:male: 2.4), with a young adulthood onset (median age: 29.5years, range: 11–68 years, interquartile range [IQR]: 38 years). At onset, 52% of TuMS patients presented with the involvement of more than one functional system and 24.5% of them with multiple TDLs. TDLs most frequently presented with an infiltrative MRI pattern (38.7%). Cerebrospinal fluid immunoglobulin G oligoclonal bands were often demonstrated (76.6%). In 25.3% of the cases, more than one acute-phase treatment was administered, and almost one-half of the patients (46.6%) were treated with high-efficacy treatments. After a median follow-up of 2.3years (range: 0.1–10.7 years, IQR: 3.4 years), the median Expanded Disability Status Scale (EDSS) score was 1.5 (range: 0–7, IQR: 2). Independent risk factors for reaching an EDSS score ≥3 were a higher age at onset (odds ratio [OR]: 1.08, 95% confidence interval [CI]: 1.03–1.14, p&nbsp

Published
2021

41. 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

42. 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

43. Altered Blood Oxygenation Level Dependent (BOLD) Cerebrovascular Reactivity in Multiple Sclerosis: Evidence for Restoration with Immunomodulation

Author

Antonio Maria Chiarelli, Alessandro Villani, Daniele Mascali, Nikolaos Petsas, Emma Biondetti, Anna Digiovanni, Eleonora Agata Grasso, Valeria Pozzilli, Paola Ajdinaj, Maria D’Apolito, Marianna Rispoli, Kevin Murphy, Carlo Pozzilli, Richard G. Wise, and Valentina Tomassini

Subjects
History, Polymers and Plastics, Business and International Management, Industrial and Manufacturing Engineering
Published
2021

44. Diagnosis and management of multiple sclerosis: MRI in clinical practice

Author

Valentina Tomassini, Julie Hall, Owen R Pearson, Joe Guadagno, Audrey Sinclair, James Overell, and Vijay Sawlani

Subjects
medicine.medical_specialty, Neurology, Monitoring, Disease, Clinical practice, State Medicine, 030218 nuclear medicine & medical imaging, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Diagnosis, medicine, Humans, Clinical significance, Medical physics, Stage (cooking), Neuroradiology, Protocol (science), Original Communication, business.industry, Management of multiple sclerosis, medicine.disease, Magnetic Resonance Imaging, Clinical Practice, Neurology (clinical), Disease-modifying treatments, business, 030217 neurology & neurosurgery, MRI
Abstract

Background Recent changes in the understanding and management of multiple sclerosis (MS) have increased the role of MRI in supporting diagnosis and disease monitoring. However, published guidelines on the use of MRI in MS do not translate easily into different clinical settings and considerable variation in practice remains. Here, informed by published guidelines for the use of MRI in MS, we identified a clinically informative MRI protocol applicable in a variety of clinical settings, from district general hospitals to tertiary centres. Methods MS specialists geographically representing the UK National Health Service and with expertise in MRI examined existing guidelines on the use of MRI in MS and identification of challenges in their applications in various clinical settings informed the formulation of a feasible MRI protocol. Results We identified a minimum set of MRI information, based on clinical relevance, as well as on applicability to various clinical settings. This informed the selection of MRI acquisitions for scanning protocols, differentiated on the basis of their purpose and stage of the disease, and indication of timing for scans. Advice on standardisation of MRI requests and reporting, and proposed timing and frequency of MRI scans were generated. Conclusions The proposed MRI protocol can adapt to a range of clinical settings, aiding the impetus towards standardisation of practice and offering an example of research-informed service improvement to support optimisation of resources. Other neurological conditions, where a gap still exists between published guidelines and their clinical implementation, may benefit from this same approach.

Published
2020

45. Predictors of training-related improvement in visuomotor performance in patients with multiple sclerosis: A behavioural and MRI study

Author

Alison E. Davidson, Eleonora Sgarlata, Valentina Tomassini, Emma C. Tallantyre, Neil Robertson, Richard G. Wise, Derek K. Jones, Rachael C. Stickland, Ilona Lipp, and Catherine Foster

Subjects
cognition, 030506 rehabilitation, medicine.medical_specialty, Multiple Sclerosis, functional recovery, Neuroimaging, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, brain plasticity, disease-modifying treatment, MRI, Multiple sclerosis, predictors, Neuroplasticity, Medicine, Humans, In patient, business.industry, Brain, Cognition, medicine.disease, Functional recovery, Hand, Magnetic Resonance Imaging, Neurology, Identification (biology), Neurology (clinical), 0305 other medical science, business, Original Research Papers, 030217 neurology & neurosurgery
Abstract

Background: The development of tailored recovery-oriented strategies in multiple sclerosis requires early identification of an individual’s potential for functional recovery. Objective: To identify predictors of visuomotor performance improvements, a proxy of functional recovery, using a predictive statistical model that combines demographic, clinical and magnetic resonance imaging (MRI) data. Methods: Right-handed multiple sclerosis patients underwent baseline disability assessment and MRI of the brain structure, function and vascular health. They subsequently undertook 4 weeks of right upper limb visuomotor practice. Changes in performance with practice were our outcome measure. We identified predictors of improvement in a training set of patients using lasso regression; we calculated the best performing model in a validation set and applied this model to a test set. Results: Patients improved their visuomotor performance with practice. Younger age, better visuomotor abilities, less severe disease burden and concurrent use of preventive treatments predicted improvements. Neuroimaging localised outcome-relevant sensory motor regions, the microstructure and activity of which correlated with performance improvements. Conclusion: Initial characteristics, including age, disease duration, visuo-spatial abilities, hand dexterity, self-evaluated disease impact and the presence of disease-modifying treatments, can predict functional recovery in individual patients, potentially improving their clinical management and stratification in clinical trials. MRI is a correlate of outcome, potentially supporting individual prognosis.

Published
2020

46. Exergames for balance dysfunction in neurological disability: a meta-analysis with meta-regression

Author

Giampaolo Brichetto, Valentina Tomassini, Davide Cattaneo, Andrea Tacchino, Claudio Solaro, Luca Prosperini, and Letizia Castelli

Subjects
medicine.medical_specialty, Neurology, Rehabilitation, business.industry, medicine.medical_treatment, medicine.disease, law.invention, Discontinuation, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Randomized controlled trial, law, Meta-analysis, Medicine, Meta-regression, 030212 general & internal medicine, Neurology (clinical), business, Adverse effect, Stroke, 030217 neurology & neurosurgery
Abstract

To evaluate systematically the efficacy of exergames for balance dysfunction in neurological conditions and to identify factors of exergaming protocols that may influence their effects. We searched electronic databases for randomized clinical trials investigating the effect of commercial exergames versus alternative interventions on balance dysfunction as assessed by standard clinical scales in adults with acquired neurological disabilities. Standardized mean differences (Hedge’s g) were calculated with random-effects models. Subgroup analyses and meta-regression were run to explore potential modifiers of effect size. Out of 106 screened articles, 41 fulfilled criteria for meta-analysis, with a total of 1223 patients included. Diseases under investigation were stroke, Parkinson’s disease, multiple sclerosis, mild cognitive impairment or early Alzheimer’s disease, traumatic brain injury, and myelopathy. The pooled effect size of exergames on balance was moderate (g = 0.43, p

Published
2020

47. Exergames for balance dysfunction in neurological disability: a meta-analysis with meta-regression

Author

Luca, Prosperini, Valentina, Tomassini, Letizia, Castelli, Andrea, Tacchino, Giampaolo, Brichetto, Davide, Cattaneo, and Claudio Marcello, Solaro

Subjects
Adult, Bias, Humans, Parkinson Disease, Nervous System Diseases, Exercise
Abstract

To evaluate systematically the efficacy of exergames for balance dysfunction in neurological conditions and to identify factors of exergaming protocols that may influence their effects.We searched electronic databases for randomized clinical trials investigating the effect of commercial exergames versus alternative interventions on balance dysfunction as assessed by standard clinical scales in adults with acquired neurological disabilities. Standardized mean differences (Hedge's g) were calculated with random-effects models. Subgroup analyses and meta-regression were run to explore potential modifiers of effect size.Out of 106 screened articles, 41 fulfilled criteria for meta-analysis, with a total of 1223 patients included. Diseases under investigation were stroke, Parkinson's disease, multiple sclerosis, mild cognitive impairment or early Alzheimer's disease, traumatic brain injury, and myelopathy. The pooled effect size of exergames on balance was moderate (g = 0.43, p 0.001), with higher frequency (number of sessions per week) associated with larger effect (β = 0.24, p = 0.01). There was no effect mediated by the overall duration of the intervention and intensity of a single session. The beneficial effect of exergames could be maintained for at least 4 weeks after discontinuation, but their retention effect was specifically explored in only 11 studies, thus requiring future investigation. Mild to moderate adverse events were reported in a minority of studies. We estimated a low risk of bias, mainly attributable to the lack of double-blindness and not reporting intention-to-treat analysis.The pooled evidence suggests that exergames improve balance dysfunction and are safe in several neurological conditions. The findings of high-frequency interventions associated with larger effect size, together with a possible sustained effect of exergaming, may guide treatment decisions and inform future research.

Published
2020

48. Characteristics and treatment of Multiple Sclerosis-related trigeminal neuralgia: An Italian multi-centre study

Author

Giorgia Teresa Maniscalco, Cinzia Cordioli, Maria Chiara Buscarinu, Diana Ferraro, Massimiliano Calabrese, Claudio Gasperini, Marcello Moccia, Alberto Gajofatto, Antonio Gallo, Eleonora Cocco, Valentina Camera, Pietro Annovazzi, Roberta Fantozzi, Marta Radaelli, Giovanna De Luca, Valentina Tomassini, Roberta Lanzillo, Claudio Solaro, Lorena Lorefice, Carla Tortorella, Federica Pinardi, Fabio Buttari, Paolo Ragonese, Paola Cavalla, Viviana Nociti, Salvatore Lo Fermo, Laura Boffa, Rirems, Damiano Paolicelli, Massimiliano Di Filippo, Ferraro, D., Annovazzi, P., Moccia, M., Lanzillo, R., De Luca, G., Nociti, V., Fantozzi, R., Paolicelli, D., Ragonese, P., Gajofatto, A., Boffa, L., Cavalla, P., Lo Fermo, S., Buscarinu, M. C., Lorefice, L., Cordioli, C., Calabrese, M., Gallo, A., Pinardi, F., Tortorella, C., Di Filippo, M., Camera, V., Maniscalco, G. T., Radaelli, M., Buttari, F., Tomassini, V., Cocco, E., Gasperini, C., Solaro, C., Ferraro D., Annovazzi P., Moccia M., Lanzillo R., De Luca G., Nociti V., Fantozzi R., Paolicelli D., Ragonese P., Gajofatto A., Boffa L., Cavalla P., Lo Fermo S., Buscarinu M.C., Lorefice L., Cordioli C., Calabrese M., Gallo A., Pinardi F., Tortorella C., Di Filippo M., Camera V., Maniscalco G.T., Radaelli M., Buttari F., Tomassini V., Cocco E., Gasperini C., and Solaro C.

Subjects
Pediatrics, medicine.medical_treatment, multiple sclerosis, microvascular decompression surgery, time factors, 0302 clinical medicine, Radiofrequency thermocoagulation, Trigeminal neuralgia, Multiple Sclerosi, Outcome Assessment, Health Care, italy, middle aged, pain, 030212 general & internal medicine, Oxcarbazepine, humans, education.field_of_study, trigeminal neuralgia, adult, Disability, Multiple Sclerosis, Pain, radiosurgery, General Medicine, Analgesics, Non-Narcotic, health care, follow-up studies, Settore MED/26 - NEUROLOGIA, aged, retrospective studies, female, Neurology, disability, analgesics, non-narcotic, male, severity of illness index, sex factors, neurosurgical procedures, outcome assessment, health care, analgesics, medicine.drug, medicine.medical_specialty, Population, Microvascular decompression, 03 medical and health sciences, medicine, education, outcome assessment, business.industry, Multiple sclerosis, Carbamazepine, medicine.disease, Discontinuation, non-narcotic, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Background The prevalence of trigeminal neuralgia (TN) in Multiple Sclerosis (MS) patients is higher than in the general population and its management can be particularly challenging. Our aim is to describe the characteristics, treatment and prognostic factors of MS-related TN in a retrospective multicentre study. Methods Neurologists members of the RIREMS group (Rising Researchers in MS) enrolled MS patients with a TN diagnosis and filled out a spreadsheet comprising their clinical data. Results Population consisted of 298 patients. First-choice preventive treatments were carbamazepine and oxcarbazepine. A surgical procedure was performed in 81 (30%) patients, most commonly gamma knife stereotactic radiosurgery (37%), followed by microvascular decompression (22%) and radiofrequency thermocoagulation (21%); one third of patients underwent at least two procedures. Surgery was associated with higher disability, male sex and longer interval between MS and TN onset. Patients (77%) who stayed on at least one preventive medication at most recent follow-up, after a mean period of 8 years, had a higher disability compared to the untreated group. Furthermore, patients with higher disability at TN onset were less likely to discontinue their first preventive medication due to pain remission, had bilateral TN more frequently and underwent surgical interventions earlier. Conclusion MS patients with a higher disability at TN onset and with a longer interval between MS and TN onset had differing clinical features and outcomes: pain was more frequently bilateral, surgery was more frequent and anticipated, and preventive medication discontinuation due to pain remission was less common.

Published
2020

49. Tractography in the presence of multiple sclerosis lesions

Author

Greg D. Parker, Alex F Goodall, Valentina Tomassini, Phoebe Heveron, Eleonora Patitucci, Derek K. Jones, Steluta Grama, Ilona Lipp, and Emma C. Tallantyre

Subjects
Adult, Male, Multiple Sclerosis, brain MRI, Cognitive Neuroscience, tractography, Biology, 050105 experimental psychology, Diffusion Anisotropy, lcsh:RC321-571, White matter, 03 medical and health sciences, 0302 clinical medicine, Fractional anisotropy, Image Interpretation, Computer-Assisted, medicine, Image Processing, Computer-Assisted, Humans, 0501 psychology and cognitive sciences, Segmentation, Computer Simulation, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, multiple sclerosis lesions, 05 social sciences, Anatomy, Middle Aged, diffusion tensor imaging, White Matter, Hyperintensity, medicine.anatomical_structure, Neurology, spherical harmonic deconvolution, Female, Deconvolution, 030217 neurology & neurosurgery, Tractography, Diffusion MRI
Abstract

Accurate anatomical localisation of specific white matter tracts and the quantification of their tract-specific microstructural damage in conditions such as multiple sclerosis (MS) can contribute to a better understanding of symptomatology, disease evolution and intervention effects. Diffusion MRI-based tractography is being used increasingly to segment white matter tracts as regions-of-interest for subsequent quantitative analysis. Since MS lesions can interrupt the tractography algorithm’s tract reconstruction, clinical studies frequently resort to atlas-based approaches, which are convenient but ignorant to individual variability in tract size and shape. Here, we revisit the problem of individual tractography in MS, comparing tractography algorithms using: (i) The diffusion tensor framework; (ii) constrained spherical deconvolution (CSD); and (iii) damped Richardson-Lucy (dRL) deconvolution. Firstly, using simulated and in vivo data from 29 MS patients and 19 healthy controls, we show that the three tracking algorithms respond differentially to MS pathology. While the tensor-based approach is unable to deal with crossing fibres, CSD produces spurious streamlines, in particular in tissue with high fibre loss and low diffusion anisotropy. With dRL, streamlines are increasingly interrupted in pathological tissue. Secondly, we demonstrate that despite the effects of lesions on the fibre orientation reconstruction algorithms, fibre tracking algorithms are still able to segment tracts that pass through areas with a high prevalence of lesions. Combining dRL-based tractography with an automated tract segmentation tool on data from 131 MS patients, the cortico-spinal tracts and arcuate fasciculi could be reconstructed in more than 90% of individuals. Comparing tract-specific microstructural parameters (fractional anisotropy, radial diffusivity and magnetisation transfer ratio) in individually segmented tracts to those from a tract probability map, we show that there is no systematic disease-related bias in the individually reconstructed tracts, suggesting that lesions and otherwise damaged parts are not systematically omitted during tractography. Thirdly, we demonstrate modest anatomical correspondence between the individual and tract probability-based approach, with a spatial overlap between 35 and 55%. Correlations between tract-averaged microstructural parameters in individually segmented tracts and the probability-map approach ranged between \ud \ud \ud \ud \ud \ud r=.53\ud (\ud \ud \ud \ud \ud \ud \ud p

Published
2020

50. q-Space Novelty Detection with Variational Autoencoders

Author

Daniel Cremers, Valentina Tomassini, Derek K. Jones, Marc Meissner, Aleksei Vasilev, Ilona Lipp, Eleonora Sgarlata, and Vladimir Golkov

Subjects
Computer science, business.industry, Deep learning, Benchmark (computing), Novelty, Inference, Pattern recognition, State (computer science), Artificial intelligence, business, Novelty detection, Class (biology), Diffusion MRI
Abstract

In machine learning, novelty detection is the task of identifying novel unseen data. During training, only samples from the normal class are available. Test samples are classified as normal or abnormal by assignment of a novelty score. The usage of deep neural networks for novelty detection remains an open challenge. Here we propose novelty detection methods based on training variational autoencoders (VAEs) on normal data. We apply these methods to magnetic resonance imaging, namely to the detection of diffusion-space (q-space) abnormalities in diffusion MRI scans of multiple sclerosis patients. q-Space novelty detection can reduce scan time duration and does not require any disease-specific prior knowledge, thus overcoming the disadvantages of other diffusion MRI processing methods. The methods proposed herein outperform the state of the art on q-space data in terms of quality and inference time. Our methods also outperform the state of the art on a standard novelty detection benchmark, and hence are also promising for non-MRI novelty detection.

Published
2020

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