Antonio Uccelli

• M.D
• Managing Director at Azienda Ospedaliera Universitaria San Martino di Genova

Background Postural instability and gait difficulties are key symptoms of Parkinson's disease (PD), elevating the risk of falls substantially. Falls afflict 35% to 90% of PD patients, representing a major challenge in managing the condition. Accurate prediction of fall risk and identification of contributing factors are essential for timely interve...

Recent sero-epidemiological studies have strengthened the hypothesis that Epstein–Barr virus (EBV) may be a causal factor in multiple sclerosis (MS). Given the complexity of the EBV–host interaction, various mechanisms may be responsible for the disease pathogenesis. Furthermore, it remains unclear whether this is a disease-specific process. Here,...

Background and purpose Neurological involvement in long COVID (coronavirus disease 2019) is well known. In a previous study we identified two subtypes of neurological long COVID, one characterized by memory disturbances, psychological impairment, headache, anosmia and ageusia, and the other characterized by peripheral nervous system involvement, ea...

Objective To investigate, in two cohorts including patients with multiple sclerosis (MS) and migraine, (i) the prevalence of the “central vein sign” (CVS), (ii) the spatial distribution of positive CVS (CVS+) lesions, (iii) the threshold of CVS+ lesions able to distinguish MS from migraine with high sensitivity and specificity. Methods A total of...

Background Alzheimer's disease (AD) is the most common form of dementia, predominantly manifesting as amnestic impairment. However, atypical presentations such as logopenic variant of primary progressive aphasia (lvPPA), posterior cortical atrophy (PCA), corticobasal syndrome (CBS) and frontal AD pose diagnostic challenges. This study presents prel...

Background The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) has been validated in many cross‐sectional studies. However, longitudinal data on BICAMS subset trajectories and their correlation with disease activity during follow‐up are scarce. Objectives We aimed to (i) assess BICAMS changes in MS patients initiating high...

This study applies the Gaussian Process Progression Model (GPPM), a Bayesian data-driven disease progression model, to analyse the evolution of primary progressive multiple sclerosis (PPMS). Utilising data from 1521 PPMS participants collected within the International Progressive MS Alliance project, the analysis includes 18,581 longitudinal time-p...

Background Magnetic resonance imaging (MRI) has recently enabled to identify four distinct Alzheimer's disease (AD) subtypes: hippocampal sparing (HpSp), typical AD (tAD), limbic predominant (Lp), and minimal atrophy (MinAtr). To date, however, the natural history of these subtypes, especially regarding the presence of subjects switching to other M...

Current technologies for precise genetic manipulation of cells often utilize site-specific recombinases, enabling the creation of conditional transgenic models for studying gene functions in specific tissues and at defined time windows. The advent of drug-inducible recombinases has further enhanced this field by allowing temporal control of gene ex...

Autoimmune encephalitis (AE) is an immune-mediated condition that induces brain inflammation due to several neural-specific autoantibodies. The main triggering and predisposing factors are infections, genetics, the use of immune checkpoint inhibitors and tumors. We report a case of a 57-year-old male with a biopsy-confirmed Langerhans cell histiocy...

Background: Arterial spin labeling (ASL) MRI has been anecdotally used to assess brain perfusion in autoimmune encephalitis (AE) and its relationship with [18F]FDG-PET dysmetabolism has been scarcely investigated.Considering the physiological coupling of metabolism and perfusion, we aimed to evaluate the degree of correspondence between ASL-MRI an...

Background The reason why some multiple sclerosis (MS) patients show disease activity after alemtuzumab (ALM) is still unclear, but ocrelizumab (OCR) could represent an interesting sequential therapeutic approach. Objectives To investigate safety and efficacy of OCR in MS patients with disease activity after two ALM courses. Methods Observational...

Objectives: Recent studies suggest that psychological resilience (PR) is associated with more well-preserved cognition in healthy subjects (HS), but an investigation of such phenomenon in patients with motor neuron diseases (MNDs) is still lacking. The aim of our study was therefore to evaluate PR and its relationship with baseline cognitive/behav...

Gut bacteria-derived metabolites, such as butyrate (BUT), shape the function of T cells through inhibition of histone deacetylases (HDAC). Natural killer (NK) cells are innate lymphocytes with important effector and regulatory functions; little is known on the effect of BUT on NK cells. Here we aimed at evaluating whether BUT affects the epigenetic...

Introduction A potential overlap in symptoms between post-acute COVID-19 syndrome and post-COVID-19 vaccination syndrome has been noted. We report a paired description of patients presenting with similar manifestations involving the central (CNS) or peripheral nervous system (PNS) following SARS-CoV-2 infection or vaccination, suggesting that both...

Objectives neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease mainly affecting optic nerves and the spinal cord. Due to the potentially irreversible tissue damage, prevention of relapses is of utmost importance. Methods We describe the atypical clinical course and pathology results of a patient with anti-aquaporin-4 antibo...

Chondroitin sulfate proteoglycans (CSPGs) are fundamental components of the extracellular matrix in the central nervous system (CNS). Among these, the Nerve-Glial antigen 2 (NG2) stands out as a transmembrane CSPG exclusively expressed in a different population of cells collectively termed NG2-expressing cells. These enigmatic cells, found througho...

Background and objectives: Retinal optical coherence tomography (OCT) provides promising prognostic imaging biomarkers for future disease activity in multiple sclerosis (MS). However, raw OCT-derived measures have multiple dependencies, supporting the need for establishing reference values adjusted for possible confounders. The purpose of this stu...

Background and purpose Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD) diagnosis are based on the presence of serological and magnetic resonance imaging (MRI) biomarkers. Diffusion tensor imaging (DTI), neurites orientation dispersion and density imaging (NODDI), and the Sph...

The NeuroArtP3 (NET-2018-12366666) is a multicenter study funded by the Italian Ministry of Health. The aim of the project is to identify the prognostic trajectories of Alzheimer's disease (AD), through the application of artificial intelligence (AI). In literature just few studies investigated the variables associated with cognitive worsening in A...

Background The burden of Parkinson Disease (PD) represents a key public health issue and it is essential to develop innovative and cost-effective approaches to promote sustainable diagnostic and therapeutic interventions. In this perspective the adoption of a P3 (predictive, preventive and personalized) medicine approach seems to be pivotal. The Ne...

Introduction Microglia and macrophages can influence the evolution of myelin lesions through the production of extracellular vesicles (EVs). While microglial EVs promote in vitro differentiation of oligodendrocyte precursor cells (OPCs), whether EVs derived from macrophages aid or limit OPC maturation is unknown. Methods Immunofluorescence analysi...

Complex diseases such as Multiple Sclerosis (MS) cover a wide range of biological scales, from genes and proteins to cells and tissues, up to the full organism. In fact, any phenotype for an organism is dictated by the interplay among these scales. We conducted a multilayer network analysis and deep phenotyping with multi-omics data (genomics, phos...

Guillain–Barré syndrome associated with Coronavirus-2-related severe acute respiratory syndrome (COV-GBS) occurs as para- or post-infectious forms, depending on the timing of disease onset. In these two forms, we aimed to compare the cerebrospinal fluid (CSF) and serum proinflammatory cytokine profiles to evaluate differences that could possibly ha...

Background Neuronal pentraxin-2 (NPTX2), crucial for synaptic functioning, declines in cerebrospinal fluid (CSF) as cognition deteriorates. The variations of CSF NPTX2 across mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and its association with brain metabolism remain elusive, albeit relevant for patient stratification and pathop...

Background Monoaminergic systems are pharmacologically modulable and therefore both a target for symptomatic therapies and a window for the study of disease progression. Although these mechanisms are unclear. We explore the progression and the distribution of monoaminergic deficits in the Alzheimer’s Disease (AD) continuum, along with the accumulat...

Background Multiple sclerosis patients would benefit from machine learning algorithms that integrates clinical, imaging and multimodal biomarkers to define the risk of disease activity. Methods We have analysed a prospective multi-centric cohort of 322 MS patients and 98 healthy controls from four MS centres, collecting disability scales at baseli...

Background Although apathy has been associated with fronto-striatal dysfunction in several neurological disorders, its clinical and magnetic resonance imaging (MRI) correlates have been poorly investigated in people with multiple sclerosis (PwMS). Objectives To evaluate clinical variables and investigate microstructural integrity of fronto-striata...

Changes is lymphocyte subpopulations in peripheral blood have been proposed as biomarkers for evaluation of disease activity in multiple sclerosis (MS). Serum neurofilament light chain (sNfL) is a biomarker reflecting neuro-axonal injury in MS that could be used to monitor disease activity, response to drugs and to prognosticate disease course. Her...

Background Acute brain injured (ABI) patients are at high risk of developing ventilator-associated pneumonia (VAP). However, incidence, risk factors and effects on outcome of VAP are not completely elucidated in this population. The primary aim of this study was to determine the incidence of VAP in a cohort of ABI patients. The secondary objectives...

Background: Although two doses of Covid-19 vaccine elicited a protective humoral response in most persons with multiple sclerosis (pwMS), a significant group of them treated with immunosuppressive disease modifying therapies (DMTs) showed less efficient responses. Methods: This prospective multiCenter observational study evaluates differences in...

Complex diseases such as Multiple Sclerosis (MS) cover a wide range of biological scales, from genes and proteins to cells and tissues, up to the full organism. We conducted a multilayer network analysis and deep phenotyping with multi-omics data (genomics, phosphoproteomics and cytomics), brain and retinal imaging, and clinical data, obtained from...

Introduction Immunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines. Methods Here we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors...

Background Multiple Sclerosis patients would benefit from machine learning algorithms that integrates clinical, imaging, and multimodal biomarkers to define the risk of disease activity. Methods We have analyzed a prospective multi-centric cohort of 322 MS patients and 98 healthy controls from four MS centers, collecting disability scales at basel...

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with no effective cure. Astrocytes display a toxic phenotype in ALS and contribute to motoneuron (MN) degeneration. Modulating astrocytes’ neurotoxicity can reduce MN death. Our previous studies showed the beneficial effect of mesenchymal stem cell (MSC) administration in SOD1G93A A...

Background In multiple sclerosis, the correlation between white matter lesion volumes (LV) and expanded disability status scale (EDSS) is at best moderate, leading to the “clinico-radiological paradox”, influenced by many factors, including the lack of information on the spatial localisation of each lesion on synthetic metrics such as LV. We used a...

Immunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines. Here we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune...

Introduction: The NeuroArtP3 (NET-2018-12366666) is a multicenter project co-funded by the Italian Ministry of Health, involving clinical and computational centers operating in the field of neurology, including neurodegenerative, neuroinflammatory and oncological diseases. The core objectives of the project are i) to harmonize the collection of dat...

Importance Despite people with impaired immune competence due to an underlying disease or ongoing therapy, hereinafter frail patients, are (likely to be) the first to be vaccinated, they were usually excluded from clinical trials. Objective To report adverse reactions of frail patients after receipt of the third dose (booster) administered after c...

The NeuroArtP3 project (NET-2018-12366666) is a 3-year multi-site research co-funded by the Italian Ministry of Health. It brings together clinical and computational Centers operating in the field of neurology, including neurodegenerative diseases. The core objectives of the project are (1) to harmonize the collection of data across the participati...

This corrects the article on p. 334 in vol. 18, PMID: 35589321.

Background In myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), several areas of demyelination are detectable in mouse cerebral cortex, where neuroinflammation events are associated with scarce inflammatory infiltrates and blood–brain barrier (BBB) impairment. In this condition, the administration of...

Background The immunotherapy strategy for autoimmune encephalitis is based on several types and schedules of both first- and second-line drugs. Failing to respond to the latter prompts the use of non-conventional rescue therapies, with higher risks of severe adverse effects. We report on a protocol that entails the use of intravenous immunoglobulin...

Treatment with fingolimod for multiple sclerosis (MS) reduces the efficacy of COVID-19 vaccination. We evaluated by a multivariate linear regression model whether main lymphocyte subsets and demographic feature correlated to the subsequent increase in anti-SARS-CoV2 antibodies following the third dose of COVID-19 vaccination in fingolimod-treated M...

Background: Natalizumab (NAT) has a strong impact on disease activity of aggressive pediatric multiple sclerosis (MS), with no difference in safety profile compared to adult MS. However, available data are limited by short follow-up. Our aim was to report long-term follow-up data (up to 11 years) of a large Italian pediatric MS cohort treated with...

Background Development of long-lasting anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) T-cell responses in persons with multiple sclerosis (pwMS) treated with ocrelizumab is questioned. Objective Investigate antiviral T-cell responses after infection with SARS-CoV-2 in ocrelizumab-treated pwMS. Control groups included ocrelizumab-...

Background Serum neurofilament light (sNfL) chain is a promising biomarker reflecting neuro-axonal injury in multiple sclerosis (MS). However, the ability of sNfL to predict outcomes in real-world MS cohorts requires further validation. Objective The aim of the study is to investigate the associations of sNfL concentration, magnetic resonance imag...

Background In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in patients with MS (pwMS) under different DMTs and to identify correlates of reduced protection. Methods This is a prospective Italian multicenter cohort study, long-term clinical follow-up of the CovaXiMS (Covid-19 vaccine in Multiple Sclerosis) study. 185...

Introduction Symptoms referable to central and peripheral nervous system involvement are often evident both during the acute phase of COVID-19 infection and during long-COVID. In this study, we evaluated a population of patients with prior COVID-19 infection who showed signs and symptoms consistent with neurological long-COVID. Methods We prospect...

Background and purpose Guillain-Barré-Syndrome (GBS) can follow COVID-19 vaccination, with clinical and paraclinical features still to be precisely assessed. We describe a cohort of patients who developed GBS after vaccination with different types of COVID-19 vaccines. Methods Patients with post-COVID-19 vaccination GBS, admitted to the six hospit...

Background and objectives: Connectivity-based approaches incorporating the distribution and magnitude of the extended brain network aberrations caused by lesions may offer higher sensitivity for axonal damage in patients with multiple sclerosis (MS) than conventional lesion characteristics. Using individual brain disconnectome mapping, we tested t...

Background: Patients with solid or hematological tumors, neurological and immune-inflammatory disorders are potentially fragile subjects at increased risk of experiencing severe COVID-19 and an inadequate response to SARS-CoV-2 vaccination. Methods: We designed a prospective Italian multicentrer study to assess humoral and T-cell responses to SA...

Background and purpose: To identify changes in the choroidal thickness (CT) in multiple sclerosis (MS) patients with and without optic neuritis (ON) using enhanced-depth-imaging optical coherence tomography (EDI-OCT). Methods: This cross-sectional study included 96 eyes with MS and 28 eyes of healthy controls. All participants underwent an ophth...

Myeloid cells, including parenchymal microglia, perivascular and meningeal macrophages, and dendritic cells (DCs), are present in the central nervous system (CNS) and establish an intricate relationship with other cells, playing a crucial role both in health and in neurological diseases. In this context, DCs are critical to orchestrating the immune...

Background One-off serum levels of neurofilament light chain (sNfL) is an established predictor of emerging disease activity in multiple sclerosis (MS). However, the importance of longitudinal increases in sNfL is yet to be enumerated, an important consideration as this test is translated for serial monitoring. Glial Fibrillary Acidic Protein (sGFA...

Background: Patients with solid or hematological tumors, neurological and immune-inflammatory disorders represent potentially fragile subjects with increased risk to experience severe COVID-19 and inadequate response to SARS-CoV2 vaccination. Methods: We designed a prospective Italian multicentric study to assess humoral and T-cell response to SARS...

Objective It is well known that spontaneous non-aneurysmal subarachnoid hemorrhage (SAH), also known as sine materia SAH (smSAH), has usually a better course and prognosis than its aneurysmal counterpart (aSAH). This might depend on different inflammatory mechanisms initiated by bleeding events of different origins. The aim of the present study was...

Background. Patients with Multiple Sclerosis (pwMS) treated with anti-CD20 or fingolimod showed a reduced humoral response to mRNA-based SARS-CoV-2 vaccines, while the degree of such responses is unimpaired and similar in pwMS treated with other disease modifying therapies (DMTs), or untreated. However, the nature of the SARS-CoV-2 vaccine-induced...

COVID 19 pandemic and mass vaccination campaigns have revealed the situation of the most vulnerable patients. In this work, we focused our attention to patients who have Multiple Sclerosis (MS), particularly in treatment with cladribine tablets, trying to understand if and when it is possible to administer the vaccine successfully. In light of the...

Background Defining immune mechanisms leading to multiple sclerosis (MS) is difficult, due to the great inter-individual difference in immune system responses. The anti-CD52 antibody alemtuzumab transiently abolishes differences in immune parameters among individuals, allowing analysis of subsequent immune cell repopulation patterns, and their poss...

Background Mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells, have been proposed as a promising therapeutic option for people with multiple sclerosis on the basis of their immunomodulatory and neuroprotective properties. The MEsenchymal StEm cells for Multiple Sclerosis (MESEMS) study was devised to evaluate the safety, tolerab...

Data regarding effectiveness and safety of ocrelizumab in the post-marking setting are lacking. The aim of our study was to provide effectiveness and safety data of ocrelizumab treatment in patients with relapsing–remitting (RR-) and progressive multiple sclerosis (PMS) and to evaluate clinical and immunological predictors of early treatment respon...

Aim We recently proposed miR-142-3p as a molecular player in inflammatory synaptopathy, a new pathogenic hallmark of multiple sclerosis (MS) and of its mouse model experimental autoimmune encephalomyelitis (EAE), that leads to neuronal loss independently of demyelination. MiR-142-3p seems to be unique among potential biomarker candidates in MS, sin...

Background: In patients with Multiple Sclerosis (pwMS) disease-modifying therapies (DMTs) affects immune response to antigens. Therefore, post-vaccination serological assessments are needed to evaluate the effect of the vaccine on SARS-CoV-2 antibody response. Methods: We designed a prospective multicenter cohort study enrolling pwMS who were sc...

Patients diagnosed with malignancy, neurological and immunological disorders, i.e., fragile patients, have been excluded from COVID-19 vaccine trials. However, this population may present immune response abnormalities, and relative reduced vaccine responsiveness. Here we review the limited current evidence on the immune responses to vaccination of...

Multiple sclerosis (MS) is a neurological disorder characterized by an autoimmune response, demyelinating plaques and axonal damage. Intense immunosuppression (II) followed by autologous hematopoietic stem cell transplantation has been proposed as a treatment in severe forms of MS. We have used murine relapsing-remitting (RR) experimental autoimmun...

We exploited genetic information to assess non-genetic influences in autoimmunity. We isolated gene modules whose products physically interact with environmental exposures related to autoimmunity, and analyzed their nominal statistical evidence of association with autoimmune and non-autoimmune diseases in genome-wide association studies (GWAS) data...

Monomethyl fumarate (MMF), metabolite of dimethyl fumarate (DMF), an immunosuppressive drug approved for the treatment of multiple sclerosis (MS), is a potent agonist for hydroxycarboxylic acid receptor 2 (HCAR2), eliciting signals that dampen cell activation or lead to inflammation such as the skin flushing reaction that is one of the main side ef...

The pathophysiological mechanisms for classical plaque characteristics and their predictive value for clinical course and outcome in multiple sclerosis is unclear. Connectivity-based approaches incorporating the distribution and magnitude of the extended brain network aberrations caused by lesions may offer higher sensitivity for axonal damage. Usi...

Deoxycytidine kinase (dCK) and 5’ deoxynucleotidase (NT5C2) are involved in metabolism of cladribine (2CdA), the immunomodulatory drug for multiple sclerosis; by mediating phosphorylation (activation) or phosphorolysis (deactivation) of 2CdA, respectively, these enzymes promote or prevent its accumulation in the cell, which leads to cell death. In...

[This corrects the article DOI: 10.3389/fnins.2020.584161.].

Neuroinflammation is associated with synapse dysfunction and cognitive decline in patients and animal models. One candidate for translating the inflammatory stress into structural and functional changes in neural networks is the transcriptional repressor RE1-silencing transcription factor (REST) that regulates the expression of a wide cluster of ne...

Objective To determine whether autologous hematopoietic stem cell transplantation (aHSCT) is able to induce durable disease remission in people with multiple sclerosis (MS), we analyzed the long-term outcomes after transplant in a large cohort of MS patients. Methods To be included, a minimum data set (consisting of age, MS phenotype, EDSS at base...

Mesenchymal stromal/stem cells (MSCs) are characterized by neuroprotective, immunomodulatory, and neuroregenerative properties, which support their therapeutic potential for inflammatory/neurodegenerative diseases, including multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). One mode of action through which MSCs exert their immunomodu...

Background: Data regarding the predictive value of optical coherence tomography (OCT)-derived measures are lacking, especially in progressive multiple sclerosis (PMS). Accordingly, we aimed at investigating whether a single OCT assessment can predict a disability risk in both relapsing-remitting MS (RRMS) and PMS. Methods: One hundred one patien...

Objective: Vasospasm is a severe complication in patients with aneurysmal subarachnoid hemorrhage (aSAH) and cannot be reliably predicted. Its pathophysiology remains elusive with the current body of evidence suggesting inflammation as one of the main driving forces. We here aimed to analyze circulating immune cell subsets over time in patients wit...

Overview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positiv...

Purpose: The incidence and the clinical presentation of neurological manifestations of coronavirus disease-2019 (COVID-19) remain unclear. No data regarding the use of neuromonitoring tools in this group of patients are available. Methods: This is a retrospective study of prospectively collected data. The primary aim was to assess the incidence and...

The CoronaVirus Disease 19 (COVID-19) pandemic is a threat of particular concern for people affected by chronic immune-mediated diseases, such as multiple sclerosis (MS), who are often treated with immunomodulatory and immunosuppressive drugs, which may increase the risk of infections in general. At the beginning of the COVID-19 pandemic, empirical...