Mauro Ceroni

• Associate Professor Neurology, MD
• Head of Department at University of Pavia

Pragmatic impairments are largely documented, yet rarely considered in clinical practice, also due to a poor characterization of pragmatic profiles across conditions, as well as some overlap with theory of mind (ToM) in the conceptualization of pragmatics. Here we present the outcome of a 10-year program that started with creating a novel test, the...

Pragmatic impairments are largely documented, yet rarely considered in clinical practice, also due to a poor characterization of pragmatic profiles across conditions, as well as some overlap with theory of mind (ToM) in the conceptualization of pragmatics. Here we present the outcome of a 10-year program that started with creating a novel test, the...

Alzheimer’s disease (AD) is a neurodegenerative disorder that progressively involves brain regions with an often-predictable pattern. Damage to the brain appears to spread and worsen with time, but the molecular mechanisms underlying the region-specific distribution of AD pathology at different stages of the disease are still under-investigated. In...

Background Alterations in EEG traces are observed in synaptic failure with a reduction in the background α rhythm and an increase in slow frequencies (θ‐δ). The aim of the study is to evaluate whether quantitative EEG (QEEG) can be a reliable biomarker of neuro‐cognitive disorders (NCD), able to identify patients with mild and major‐NCD, and to ref...

Background Few studies investigate the correlation between the quantitative EEG (QEEG) and the neuropathological picture. The purpose of this study is to explore how QEEG can recognize the type and extent of neuropathological changes. Method The EEG traces and brains belonging to 14 donors of the Abbiategrasso Brain Bank were analyzed. The subject...

Here, we aim to describe COVID-19 pathology across different tissues to clarify the disease’s pathophysiology. Lungs, kidneys, hearts, and brains from nine COVID-19 autopsies were compared by using antibodies against SARS-CoV-2, macrophages-microglia, T-lymphocytes, B-lymphocytes, and activated platelets. Alzheimer’s Disease pathology was also asse...

Alzheimer’s disease (AD) and Lewy body dementia (LBD) are two different forms of dementia, but their pathology may involve the same cortical areas with overlapping cognitive manifestations. Nonetheless, the clinical phenotype is different due to the topography of the lesions driven by the different underlying molecular processes that arise apart fr...

Background Alzheimer’s disease (AD) and Lewy body dementia (LBD) are two different forms of dementia, but their pathology may involve the same cortical areas with overlapping cognitive manifestation. Dementia cases within the same family share a common genetic background. Nonetheless, the clinical phenotype may be different due to the different und...

Objectives There is a lack of effective biomarkers for neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia. Extracellular vesicle (EV) RNA cargo can have an interesting potential as a non-invasive biomarker for NDs. However, the knowledge about...

Importance Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective To identify the genetic variants associated with juvenile ALS. Design, Setting, and Participants In this multicenter family-based genetic study, trio whole-exome sequencing was...

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. Although its etiology is still unknown, many genes have been found to be implicated in ALS pathogenesis. The Cu/Zn superoxide dismutase (SOD1) gene was the first to be identified. Currently, more than 230 mutations in the SOD1 gene have been reported....

Since the association of SARS-Cov-2 infection with Nervous System (NS) manifestations, we performed RNA-sequencing analysis in Frontal Cortex of COVID-19 positive or negative individuals and affected or not by Dementia individuals. We examined gene expression differences in individuals with COVID-19 and Dementia compared to Dementia only patients b...

Importance Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective To identify the genetic variants associated with juvenile ALS. Design, Setting, and Participants In this multicenter family-based genetic study, trio whole-exome sequencing w...

The actual role of SARS‐CoV‐2 in brain damage remains controversial due to lack of matched controls. We aim to highlight to what extent is neuropathology determined by SARS‐CoV‐2 or by pre‐existing conditions. Findings of 9 Coronavirus disease 2019 (COVID‐19) cases and 6 matched non‐COVID controls (mean age 79 y/o) were compared. Brains were analyz...

SARS-Cov-2 infection is frequently associated with Nervous System manifestations. However, it is not clear how SARS-CoV-2 can cause neurological dysfunctions and which molecular processes are affected in the brain. In this work, we examined the frontal cortex tissue of patients who died of COVID-19 for the presence of SARS-CoV-2, comparing qRT-PCR...

Identifying biomarkers is essential for early diagnosis of neurodegenerative diseases (NDs). Large (LEVs) and small extracellular vesicles (SEVs) are extracellular vesicles (EVs) of different sizes and biological functions transported in blood and they may be valid biomarkers for NDs. The aim of our study was to investigate common and different miR...

Objective Few studies have examined lockdown effects on the way of living and well-being of older adults stratified by cognitive state. Since cognitive deficits are common in this population, we investigated how cognition influenced their understanding of the pandemic, socio-behavioral responses and lifestyle adaptations during lockdown, and how th...

Background Frontotemporal Spectrum Disorder (FTSD) and Amyotrophic Lateral Sclerosis (ALS) are neurodegenerative diseases often considered as a continuum from clinical, epidemiologic, and genetic perspectives. We used localized brain volume alterations to evaluate common and specific features of FTSD, FTSD-ALS, and ALS patients to further understan...

Background Identifying robust biomarkers is essential for early diagnosis of neurodegenerative diseases (NDs). Large (LEVs) and small extracellular vesicles (SEVs) are extracellular vesicles (EVs) of different sizes and biological functions transported in blood and they may be valid biomarkers for NDs. The aim of our study was to investigate common...

During the recent coronavirus disease 2019 (COVID-19) outbreak in Northern Italy, we observed a 57-year-old man developing acute motor-sensory axonal neuropathy, a variant of Guillain–Barré syndrome (GBS), 12 days after severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Similarly to other bacterial and viral infections, dysregu...

Background Amyotrophic Lateral Sclerosis (ALS) was traditionally described as a disease restricted to the motor system. However, recent findings suggested that it also affects cognition, especially executive functions, social cognition, language and pragmatics. A relevant issue in current research is thus the description of the cognitive phenotype...

Background Delirium may be one of the presenting symptoms of COVID-19, complicating diagnosis and care of elderly patients with dementia. We aim to identify the prevalence and prognostic significance of delirium as the sole onset manifestation of COVID-19. Methods This is a retrospective single-centre study based on review of medical charts, condu...

Conflicting results about alterations of plasma amino acid (AA) levels are reported in subjects with Alzheimer’s disease (AD). The current study aimed to provide more homogeneous AA profiles and correlations between AAs and cognitive tests. Venous plasma AAs were measured in 54 fasting patients with AD (37 males, 17 females; 74.63 ± 8.03 yrs; 3.2 ±...

Chapter to be included in the volume Pragmatic Language Disorders: Complex and Underserved Populations, Ed. Louise Cummings, Springer, 2020. It reviews findings that have contributed to our understanding of pragmatic impairment in ALS.

Objective: Frontotemporal Lobe Degeneration (FTLD) and Amyotrophic Lateral Sclerosis (ALS) are neurodegenerative diseases more often considered as a continuum from clinical, epidemiologic and genetic perspectives. We used localized brain atrophy to evaluate common and specific features of FTLD, FTLD-ALS and ALS patients to clarify this clinical con...

The use of biomarkers has recently supported the association between Alzheimer disease (AD) pathology and the logopenic variant of primary progressive aphasia (PPA). We aim to investigate possible differences in cerebrospinal fluid (CSF) biomarker concentrations in the three PPA variants, and to assess any agreement between CSF biomarkers and (18)F...

We already demonstrated that in peripheral blood mononuclear cells (PBMCs) of sporadic amyotrophic lateral sclerosis (sALS) patients, superoxide dismutase 1 (SOD1) was present in an aggregated form in the cytoplasmic compartment. Here, we investigated the possible effect of soluble SOD1 decrease and its consequent aggregation. We found an increase...

Introduction Disruptions of proteasome and autophagy systems are central events in amyotrophic lateral sclerosis (ALS) and support the urgent need to find therapeutic compounds targeting these processes. The heat shock protein B8 (HSPB8) recognises and promotes the autophagy-mediated removal of misfolded mutant SOD1 and TDP-43 fragments from ALS mo...

The lack of biomarkers in Amyotrophic Lateral Sclerosis (ALS) makes it difficult to determine the stage of the disease in patients and, therefore, it delays therapeutic trials. Microvesicles (MVs) are possible biomarkers implicated in physiological and pathological functions, however, their role in ALS remains unclear. We investigated whether plasm...

Western blot analysis of co-immunoprecipitation of CD45+ MVs with misfolded SOD1 and TDP-43 of Figure 3A. Immunoblots of MVs (input), immunoprecipitated CD45+ MVs (Bound) and of CD45- MVs (Unbound) from plasma of an healthy donor (CTRL1-lane 1, 4, 7) and two ALS patients (ALS 1-lane 2, 5, 8) and ALS 2-lane 3, 6, 9) with rabbit anti CD45 antibody (A...

Microvesicles isolation. (A) Representative image of MVs (2 MVs of about 150 nm) from plasma obtained by transmission electron microscopy (TEM) (Scale bar: 100 nm); (B) Nanoparticle distribution by NTA confirmed the purity of MVs (mode = 137.8 +/- 6.0 nm) (C) Western Blot of MVs and EXOs markers in MVs and EXOs samples showed the presence of Annexi...

Leukocyte derived MVs are enriched in ALS patients with a different trend from endothelial, platelet and erythrocyte derived MVs. The histogram represents the enrichment of CD45, CD31, CD61, and CD235a MVs in four representative ALS patients and CTRLs (A). Flow cytometry dot plots of MVs isolated from plasma of a representative ALS patient labelled...

Coding and long non-coding RNA (lncRNA) metabolism is now revealing its crucial role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. In this work, we present a dataset obtained via Illumina RNA-seq analysis on Peripheral Blood Mononuclear Cells (PBMCs) from sporadic and mutated ALS patients (mutations in FUS, TARDBP, SOD1 and VCP genes) and he...

Our current knowledge of the structure, function, and diseases of the brain comes from direct examination of its substance. In the last centuries, only a few elite had managed to retrieve, gather, and preserve the elusive brain for their own research. The resulting brain collections, stored in formalin-filled jars or dried up in cabinets, served an...

It is evident to everyone, even to non-professionals, that human consciousness raises a major problem in Science and therefore in Neuroscience. So much so that today we try in every way to eliminate consciousness as pure epiphenomenon or to completely reduce it to the brain. The article specifies first the scientific method and discusses the possib...

Background Patients with history of brain radiotherapy can experience acute “stroke‐like” syndromes related to the delayed effects of brain radiation, including “Stroke‐like Migraine Attacks after Radiation Therapy (SMART)”, “Peri‐Ictal Pseudoprogression (PIPG)”, and “Acute Late‐onset Encephalopathy after Radiation Therapy (ALERT)” syndrome. The ai...

Figure S1. The concentrations of neurofilament isoforms are shown for patients with ALS and controls for (A) NfL [g/L], (B) NfM [g/L] and (C) NfH [g/L].

Table S1. Protocol for the NfH ELISA. Table S2. Clinical features and exposure: fast versus slow progressors. Continuous variables were presented with median (IQR). Table S3. Summary of plasma concentration of NfL, NfM, and NfH in ALS patients and in controls. Plasma Nf levels of controls and ALS clinical subgroups were presented as Median (IQR).

Amyotrophic lateral sclerosis (ALS) is a progressive adult-onset neurodegenerative disease, that affects cortical, bulbar and spinal motor neurons, and it is considered a proteinopathy, in which pathological proteins (SOD1, TDP-43, and FUS) may accumulate and interfere with neuronal functions eventually leading to cell death. These proteins can be...

Paraneoplastic neurological syndromes are very rare and often associated to breast, ovarian and small cells lung cancers. Paraneoplastic motor neuron diseases (MNDs) are even rarer, and frequently described in patients with breast cancer. We presented the first case of patient affected by HER2-positive breast tumor and possible paraneoplastic lower...

Neurofilament proteins (Nf) are a biomarker of disease progression in amyotrophic lateral sclerosis (ALS). This study investigated whether there are major differences in expression from in vivo measurements of neurofilament isoforms, from the light chain, NfL (68 kDa), compared to larger proteins, the medium chain (NfM, 150 kDa) and the heavy (NfH,...

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin f...

Alteration in RNA metabolism, concerning both coding and long non-coding RNAs (lncRNAs), may play an important role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. In this work, we performed a whole transcriptome RNA-seq analysis to investigate the regulation of non-coding and coding RNAs in Sporadic ALS patients (SALS), mutated ALS patients (...

New evidences switch the hypothesis of amyotrophic lateral sclerosis (ALS) from a "neurocentric" to a "multisystemic" or "non-neurocentric" point of view. From 2006, we focused on the study of non-neural cells, patients' peripheral blood mononuclear cells (PMBCs) and lymphoblastoid cell lines (LCLs). Here, we characterized LCLs of sporadic ALS and...

Background Transverse myelitis (TM) is an inflammatory disorder that can be idiopathic or associated with central nervous system autoimmune/dysimmune inflammatory diseases, connective tissue autoimmune diseases, or post-infectious neurological syndromes. Prognosis of initial TM presentations is uncertain. Objective To identify outcome predictors i...

To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1...

To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1...

Combined central and peripheral demyelination (CCPD) is rare, and current knowledge is based on case reports and small case series. The aim of our study was to describe the clinical features, diagnostic results, treatment and outcomes in a large cohort of patients with CCPD. Thirty-one patients entered this retrospective, observational, two-center...

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that affects central and peripheral motor neuron cells. Its etiology is unknown, although a relationship between genetic background and environmental factors may play a major role in triggering the neurodegeneration. In this review, we analyze the role of environmental factor...

Bone Marrow Transplantation is a high quality, peer-reviewed journal covering all aspects of clinical and basic haemopoietic stem cell transplantation.

A healthy 29-year-old man suffered from adult-onset epilepsy, characterized by polymorphic progressive seizures resistant to AEDs, leading to unilateral cortical deficits and atrophy of the left hemisphere. The disorder satisfied the clinical, EEG, and imaging criteria for a diagnosis of Rasmussen's encephalitis. During the acute phase of the disea...

Dear Sirs,Amyotrophic lateral sclerosis (ALS) is a late-onset disease caused by motor neuron degeneration with no effective therapies [1]. Approximately, 5-10 % of cases are familial (FALS), whereas the majority of patients are sporadic (SALS). ALS exhibits an extreme genetic heterogeneity and at least 25 genes are associated to familial forms, wit...

Neoplastic meningitis is a central nervous system complication that occurs in 3-5% of patients with cancer. Although most commonly seen in patients with disseminated disease, in a small percentage of patients, it may be the initial manifestation of cancer or even primitive in origin. In the absence of cancer history, the diagnosis of neoplastic men...

INTRODUCTION: Allogeneic bone marrow transplantation (BMT) has now become a common procedure in the treatment of a variety of hematologic disorders. Neurological complications after BMT are a frequent event, including subtle relapses of hematologic malignancy and a number of pleomorphic conditions, ranging from CNS infections to cerebrovascular dis...

Objectives In recent years, herpes simplex encephalitis (HSE) has been reported with increasing frequency in settings of immunosuppression, such as acquired immunodeficiency, transplantation and cancer. As observed, in immunocompromised individuals HSE presents peculiar clinical and paraclinical features, and poorer prognosis. Methods Here we descr...

To investigate the molecular defect underlying a large Italian kindred with progressive adult-onset respiratory failure, proximal weakness of the upper limbs, and evidence of lower motor neuron degeneration. We describe the clinical features of 5 patients presenting with prominent respiratory insufficiency, proximal weakness of the upper limbs, and...

Objective: To assess whether physical activity is a risk factor for amyotrophic lateral sclerosis (ALS). Methods: From February 2008 to April 2012, 652 patients with ALS from European population-based registries (France, Ireland, Italy, United Kingdom, Serbia) and 1,166 population controls (matched for age, sex, and residency) were assessed. Upon d...

Tumoral neoangiogenesis characterizes high grade gliomas. Relative Cerebral Blood Volume (rCBV), calculated with Dynamic Susceptibility Contrast (DSC) Perfusion-Weighted Imaging (PWI), allows for the estimation of vascular density over the tumor bed. The aim of the study was to characterize putative tumoral neoangiogenesis via the study of maximal...

Abstract OBJECTIVE: To determine the long-term survival in amyotrophic lateral sclerosis (ALS) and identify predictors of prolonged survival in a population-based cohort of newly diagnosed patients. METHODS: An incident cohort from a population-based registry during the years 1998 through 2002 in Lombardy, Italy was followed until death or to Febr...

Identification of mutations at familial loci for amyotrophic lateral sclerosis (ALS) has provided novel insights into the aetiology of this rapidly progressing fatal neurodegenerative disease. However, genome-wide association studies (GWAS) of the more common (∼90%) sporadic form have been less successful with the exception of the replicated locus...

Recent data suggest that circulating endothelial and progenitor cells (CECs and CEPs, respectively) may have predictive potential in cancer patients treated with bevacizumab, the antibody recognizing vascular endothelial growth factor (VEGF). Here we report on CECs and CEPs investigated in 68 patients affected by recurrent glioblastoma (rGBM) treat...