Alessandro Padovani

• MD, PhD
• Head of Faculty at University of Brescia

Background There is a need for simplified classification systems capable of effectively stratifying Parkinson’s disease (PD) in routine clinical practice. Objectives Identification of PD subtypes integrating neuroimaging and clinical features, widely used to support clinical diagnosis. Methods We included, from Parkinson’s Progression Markers Ini...

Alcohol, coffee, and tobacco consumption was assessed on 151 FTD outpatients and 151 matched controls in a multicenter retrospective case-control design. No association was found for smoking and coffee intake. The risk of FTD was decreased by alcohol consumption (adj. OR 0.30, 95% CI 0.14–0.63); risk reduction was significant in current alcohol con...

In light of future pharmacological interventions, neuroimaging markers able to assess the response to treatment would be crucial. In Granulin (GRN) disease, preclinical data will prompt pharmacological trials in the future. Two main points need to be assessed: 1) to identify target regions in different disease stages and 2) to determine the most ac...

Background Genetic testing of familial Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) is attracting interest thanks to innovative primary prevention clinical trials and increased request for information by at-risk individuals. However, ethical, social, and psychological implications are paramount and genetic testing must be s...

Frontotemporal dementia (FTD) is characterized by executive dysfunctions, behavioral disturbances, language deficits and extrapyramidal symptoms. Frontotemporal lobar degeneration-modified Clinical Dementia Rating Scale (FTLD modified-CDR) has been proposed to measure disease severity in behavioral variant FTD (bvFTD). No tools of global disease se...

Background Considering the increasing evidence that disease-modifying treatments for Alzheimer’s disease (AD) must be administered early in the disease course, the development of diagnostic tools capable of accurately identifying AD at early disease stages has become a crucial target. In this view, transcranial magnetic stimulation (TMS) has become...

Vascular risk factors have been associated with cognitive deficits and incident dementia in the general population, but their role on cognitive dysfunction in Parkinson’s disease (PD) is still unclear. The present study addresses the single and cumulative effect of vascular risk factors on cognition in PD patients, taking clinical confounders into...

ABSTRACT Background Functional motor disorders (FMD) are a frequent neurological condition affecting patients with movement disorders. Commonly described in younger adults, their manifestation can be also associated to an elderly onset. Objective To assess the prevalence and describe the clinical manifestations of FMD with elderly and younger onse...

INTRODUCTION We assessed TAR DNA‐binding protein 43 (TDP‐43) seeding activity and aggregates detection in olfactory mucosa of patients with frontotemporal lobar degeneration with TDP‐43‐immunoreactive pathology (FTLD‐TDP) by TDP‐43 seeding amplification assay (TDP43‐SAA) and immunocytochemical analysis. METHODS The TDP43‐SAA was optimized using fr...

Amyloidoses represent a group of diseases characterized by the pathological accumulation in the extracellular area of insoluble misfolded protein material called “amyloid”. The damage to the tissue organization and the direct toxicity of the amyloidogenic substrates induce progressive dysfunctions in the organs involved. They are usually multisyste...

Background Gamma (γ) brain oscillations are dysregulated in Alzheimer’s disease (AD) and can be modulated using transcranial alternating stimulation (tACS). In the present paper, we describe the rationale and design of a study assessing safety, feasibility, clinical and biological efficacy, and predictors of outcome of a home-based intervention con...

Introduction Safinamide is a recent antiparkinsonian drug that modulates both dopaminergic and glutamatergic systems with positive effects on motor and nonmotor symptoms of Parkinson’s disease (PD). Here, we aimed to describe the efficacy and safety of safinamide in the Italian PD patients in real-life conditions. Methods We performed a sub-analys...

The extent of nerve involvement in leprosy is highly variable in distribution and clinical presentation. Mononeuropathies, multiple mononeuropathies, and polyneuropathies can present both in the context of a cutaneous and/or systemic picture and in the form of pure neuritic leprosy (PNL). The differential diagnosis of leprosy neuropathy remains cha...

Background: Hematoma expansion (HE) is common and predicts poor outcome in patients with supratentorial intracerebral hemorrhage (ICH). We investigated the predictors and prognostic impact of HE in infratentorial ICH. Methods: We conducted a retrospective analysis of patients with brainstem and cerebellar ICH admitted at seven sites. Noncontrast...

Introduction: Brain hypometabolism patterns have been previously associated with cognitive decline in Parkinson's disease (PD). Our aim is to evaluate the impact of single-subject fluorodeoxyglucose (FDG)-PET brain hypometabolism on long-term cognitive and motor outcomes in PD. Methods: Forty-nine non-demented PD patients with baseline brain FDG-P...

Backgrounds Delirium is a common event among Covid-19 hospitalized patients. In this work, we aim at evaluate the predictors of delirium and its impact on mortality and disability in Covid-19 patients. Methods Two thousand two hundred eighty-eight Covid-19 patients were admitted to Brescia hospital from 2020 to 2022. Clinical and laboratory feature...

Background To date, there are no large studies delineating the clinical correlates of “pure” essential tremor (ET) according to its new definition. Methods From the ITAlian tremor Network (TITAN) database, we extracted data from patients with a diagnosis of “pure” ET and excluded those with other tremor classifications, including ET-plus, focal, a...

Pompe disease (PD) is an autosomal recessive disorder caused by mutations in the GAA gene that lead to a deficiency in the acid alpha-glucosidase enzyme. Two clinical presentations are usually considered, named infantile-onset Pompe disease (IOPD) and late-onset Pompe disease (LOPD), which differ in age of onset, organ involvement, and severity of...

Background and objective Hematoma expansion (HE) is a major determinant of neurological deterioration and poor outcome in intracerebral hemorrhage (ICH) and represents an appealing therapeutic target. We analyzed the prognostic effect of different degrees of HE. Methods retrospective analysis of ICH patients admitted at eight academic institutions...

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a rare autosomal recessive long-chain fatty acid oxidation disorder caused by mutations in the ACADVL gene. The myopathic form presents with exercise intolerance, exercise-related rhabdomyolysis, and muscle pain, usually starting during adolescence or adulthood. We report on a 17-year-old...

Unlabelled: The MUNIX technique allows us to estimate the number and size of surviving motor units (MUs). Previous studies on ALS found correlations between MUNIX and several clinical measures, but its potential role as a predictor of disease progression rate (DPR) has not been thoroughly evaluated to date. We aimed to investigate MUNIX's ability...

Background and objectives Choroid plexus (ChP) is emerging as a key brain structure in the pathophysiology of neurodegenerative disorders. In this observational study we investigated ChP volume in a large cohort of frontotemporal lobar degeneration (FTLD) spectrum patients to explore a possible link between ChP volume and other disease-specific bio...

Mobility is defined as the ability to independently move around in the environment; it is a strong prognostic marker for disability and mortality in the general population, and it is a key contributor to quality of life, especially in older age. The digital assessment of mobility has been recently recognized as pivotal endpoint for pharmacological...

The increasing percentage of patients affected by dementia calls for effective cognitive screening in healthcare in order to identify early signs of cognitive neurodegeneration which could possibly lead to early intervention. Characteristic of new Digitized Cognitive Assessment (DCA) is the ability to provide accurate measurement of more variables....

Background and Objective A variety of neurological disorders has been reported as presentations or complications of COVID-19 infection. The objective of this study was to determine their incidence dynamics and long-term functional outcome. Methods The Neuro-COVID Italy study was a multicentre, observational, cohort study with ambispective recruitm...

Background: Brain imaging with [18F]FDG-PET can support the diagnostic work-up of patients with α-synucleinopathies. Validated data analysis approaches are necessary to evaluate disease-specific brain metabolism patterns in neurodegenerative disorders. This study compared the univariate Statistical Parametric Mapping (SPM) single-subject procedure...

ALCAR (Acetyl-L-carnitine) is a donor of acetyl groups and increases the intracellular levels of carnitine, the primary transporter of fatty acids across the mitochondrial membranes. In vivo studies showed that ALCAR decrease oxidative stress markers and pro-inflammatory cytokines. In a previous double-blind placebo-controlled phase II trial showed...

Cerebellar transcranial direct current stimulation (tDCS) represents a promising therapeutic approach for both motor and cognitive symptoms in neurodegenerative ataxias. Recently, transcranial alternating current stimulation (tACS) was also demonstrated to modulate cerebellar excitability by neuronal entrainment. To compare the effectiveness of cer...

Introduction: Idiopathic REM sleep Behavior Disorder (iRBD) is a condition at high risk of developing Parkinson’s disease (PD) and other alpha-synucleinopathies. Aim of the study was to evaluate subtle turning alterations by using Mobile health technology (MHT) in iRBD individuals without subthreshold parkinsonism. Methods A total of 148 participan...

Background Graph theory models a network by its nodes and connections. “Degree” hubs reflect node centrality, while “connector” hubs are those linked to several clusters of nodes. Here we compared hubs modelled from measures of interdependencies of between‐electrode resting‐state eyes‐closed electroencephalography (rsEEG) rhythms in normal old (Nol...

Background: Data regarding the importance of multidimensional frailty to guide clinical decision making for remdesivir use in older patients with coronavirus disease 2019 (COVID-19) are largely unexplored. Objective: The aim of this research was to evaluate if the Multidimensional Prognostic Index (MPI), a multidimensional frailty tool based on...

Background: Alterations in time awareness have been reported in dementia, particularly in Alzheimer's disease (AD) and frontotemporal dementia (FTD). However, the neurophysiological correlates underlying these alterations remain largely unexplored. This study aimed to investigate the neurophysiological correlates of altered time awareness in AD an...

Objectives: Non-contrast computed tomography (NCCT) markers are robust predictors of parenchymal hematoma expansion in intracerebral hemorrhage (ICH). We investigated whether NCCT features can also identify ICH patients at risk of intraventricular hemorrhage (IVH) growth. Methods: Patients with acute spontaneous ICH admitted at four tertiary cen...

It is well established that neurological and non-neurological autoimmune disorders can be triggered by viral infections. It remains unclear whether SARS-CoV-2 infection induces similar conditions and whether they show a distinctive phenotype. We retrospectively identified patients with acute inflammatory CNS conditions referred to our laboratory fo...

Introduction: Accumulating evidence suggests that α-synuclein (αSyn) can modulate Alzheimer's disease (AD) pathology. The aim of this study was to evaluate the prevalence and clinical features associated with cerebrospinal fluid (CSF) αSyn detected by seed amplification assay (SAA) in AD. Methods: Eighty AD patients with CSF AT(N) biomarker posi...

Perihaematomal oedema is a potential therapeutic target to improve outcome of patients with intracerebral haemorrhage, but its pathophysiology remains poorly elucidated. We investigated the longitudinal changes of cerebral perfusion and their influence on perihaematomal oedema development in 150 patients with intracerebral haemorrhage who underwent...

Background: There is a need to better understand the rate of cognitive and motor decline of Dementia with Lewy bodies (DLB) and Parkinson's disease Dementia (PDD). Objectives: To compare the rate of cognitive and motor decline in patients with DLB and PDD from the E-DLB Consortium and the Parkinson's Incidence Cohorts Collaboration (PICC) Cohort...

Introduction: The impairment of nigrostriatal dopaminergic network is a core feature of dementia with Lewy bodies (DLB). The involvement and reconfiguration of extranigrostriatal dopaminergic circuitries in the DLB continuum is still theme of debate. We aim to investigate in vivo the dynamic changes of local and long-distance dopaminergic networks...

Background: Based on their pharmacological target, two classes of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) have been identified: antibodies against the CGRP ligand - Galcanezumab, Fremanezumab, Eptinezumab - and the CGRP receptor (CGRP-R), Erenumab. Aim of the present study was to compare anti-CGRP versus anti-CGRP-R mAb...

Background: Neurotransmitters deficits in Frontotemporal Dementia (FTD) are still poorly understood. Better knowledge of neurotransmitters impairment, especially in prodromal disease stages, might tailor symptomatic treatment approaches. Methods: In the present study, we applied JuSpace toolbox, which allowed for cross-modal correlation of Magne...

Background: The aim of the present study was to assess the migraine outcome, in particular migraine disability, in chronic (CM) and high frequency episodic migraine (HFEM) patients in treatment with galcanezumab. Methods: The present study was conducted at the Headache Centre of Spedali Civili of Brescia. Patients were treated with galcanezumab 120...

Background Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease whose spreading and progression mechanisms are still unclear. The ability to predict ALS prognosis would improve the patients’ quality of life and support clinicians in planning treatments. In this paper, we investigate ALS evolution trajectories using Process Mining (PM)...

Background: Effects of dopaminergic medications used to treat Parkinson's disease (PD) may be compared with each other by using conversion factors, calculated as Levodopa equivalent dose (LED). However, current LED proposals on MAO-B inhibitors (iMAO-B) safinamide and rasagiline are still based on empirical approaches. Objectives: To estimate LE...

Background: Intracerebral hemorrhage (ICH) has high mortality in the acute phase, and poor functional outcome in the majority of survivors. ICH recurrence is a major determinant of long term prognosis and is the most feared complication of antithrombotic treatment. On the other hand, ICH patients are at high risk of future ischemic vascular events...

Importance Diagnostic incidence data for syndromes associated with frontotemporal lobar degeneration (FTLD) in multinational studies are urgent in light of upcoming therapeutic approaches. Objective To assess the incidence of FTLD across Europe. Design, Setting, and Participants The Frontotemporal Dementia Incidence European Research Study (FRONT...

Introduction: Graph theory models a network by its nodes (the fundamental unit by which graphs are formed) and connections. 'Degree' hubs reflect node centrality (the connection rate), while 'connector' hubs are those linked to several clusters of nodes (mainly long-range connections). Methods: Here, we compared hubs modeled from measures of int...

Background and objectives Sex is an important contributing factor to neuroimaging phenotypes in brain disorders. However, little is known about the contribution of sex differences to the neurodegeneration in dementia with Lewy bodies (DLB). We investigated sex differences in probable DLB patients by using both visual rating scales of lobar atrophy...

Background: Intracranial carotid artery calcifications (ICAC) are a common finding on non-contrast computed tomography (NCCT) and have been associated with an increased risk of ischemic stroke. However, no data are available about the association between ICAC patterns and stroke etiology. We investigated the association between ICAC patterns and e...

Background Calcitonin gene-related peptide (CGRP) plays a pivotal role in migraine physiology, not only regarding migraine pain but also associated symptoms such as photophobia. The aim of the present study was to assess monoclonal antibodies targeting CGRP efficacy not only in terms of headache and migraine frequency and disability but also in red...

Primary progressive aphasias (PPAs) are a group of neurodegenerative diseases mainly characterized by language impairment, and with variably presence of dysexecutive syndrome, behavioural disturbances and parkinsonism. Detailed knowledge of neurotransmitters impairment and its association with clinical features hold the potential to develop new tai...

BACKGROUND Noncontrast computed tomography hypodensities are a validated predictor of hematoma expansion (HE) in intracerebral hemorrhage and a possible alternative to the computed tomography angiography (CTA) spot sign but their added value to available prediction models remains unclear. We investigated whether the inclusion of hypodensities impro...

The aim of the present study was to assess erenumab efficacy in migraine disability and intensity throughout the first treatment cycle, discontinuation, and the first 6 months of re-treatment in patients with high-frequency episodic migraine. The study design was retrospective and observational. Inclusion criteria were the following: diagnosis of h...

Background In recent years, neuroimaging with deep learning (DL) algorithms have made remarkable advances in the diagnosis of neurodegenerative disorders. However, applying DL in different medical domains is usually challenged by lack of labeled data. To address this challenge, transfer learning (TL) has been applied to use state-of-the-art convolu...

Introduction Functional Motor Disorders (FMDs) represent nosological entities with no clear phenotypic characterization, especially in patients with multiple (combined FMDs) motor manifestations. A data-driven approach using cluster analysis of clinical data has been proposed as an analytic method to obtain non-hierarchical unbiased classifications...

Background: Hematoma expansion (HE) is an appealing therapeutic target in intracerebral hemorrhage (ICH) and non-contrast computed tomography (NCCT) features are promising predictors of HE. Aims: We investigated whether onset-to-CT time influences the diagnostic performance of NCCT markers for HE. Methods: retrospective multicentre analysis of pati...

Background: Genome-wide Association Studies (GWAS) have reshaped our understanding of the genetic bases of complex diseases in general and neurodegenerative diseases in particular. Despite being a common disorder, dementia with Lewy bodies (DLB), which, together with Parkinson's disease dementia (PDD), comprise the umbrella term Lewy body dementias...

A new study provides evidence for an association between COVID-19 and long-term neurological syndromes. The findings highlight the need for further research into the long-term neurological consequences of SARS-CoV-2 infection and the development of strategies that lessen the effects of these consequences on patient quality of life and on healthcare...

In recent years, muscle imaging has become a fundamental add-on in the diagnostic process of subjects with neuromuscular diseases. Even considering its high costs, magnetic resonance imaging (MRI) is undoubtly the modality of choice for imaging muscles and nerves, due to its noninvasiveness and high spatial and resolution contrast.The possibility t...

Background: Pisa syndrome (PS) and camptocormia (CC) are postural abnormalities frequently associated with Parkinson's disease (PD). Their pathophysiology remains unclear, but the role of cognitive deficits has been postulated. Objectives: To identify differences in the neuropsychological functioning of patients with PD with PS or CC compared wi...

Background The role of vaccination on Covid-19 severity in neurological patients is still unknown. We aim at describing clinical characteristics and outcomes of breakthrough and unvaccinated Covid-19 patients hospitalized for neurological disorders. Methods Two hundred thirty-two Covid-19 patients were admitted to a neuro-Covid Unit form March 2021...

Primary progressive aphasias (PPAs) are a group of neurodegenerative diseases mainly characterized by language impairment, and with variably presence of dysexecutive syndrome, behavioural disturbances and parkinsonism. Detailed knowledge of neurotransmitters impairment and its association with clinical features hold the potential to develop new tai...

Intracranial carotid artery calcifications (ICAC) are a common finding on non-contrast computed tomography (NCCT) and have been associated with an increased risk of ischemic stroke. Intimal, medial, and mixed subtypes of ICAC have been recognized, but no data are available about the association between ICAC patterns and stroke etiology. The aim of...

The aim of this study is to assess changes in the body distribution and the semeiology of functional motor disorder (FMD) in patients who reported only one or more than one body site affected at FMD onset. Data were obtained from the Italian Registry of Functional Motor Disorders, which included patients with a diagnosis of clinically definite FMDs...

Introduction: despite neurofilaments are mainly expressed in large caliber myelinated axons, recent evidence supports the existence of a specific synaptic pool, where neurofilament light chain (NfL) has been proposed to stabilize NMDAR at post-synaptic membrane through a direct interaction with the GluN1 subunit. Here, we assessed the expression a...

Previous evidence suggests that the derangement of large-scale brain networks reflects structural, molecular, and functional mechanisms underlying neurodegenerative diseases. Although the alterations of multiple large-scale brain networks in Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) are reported, a comprehensive study on connecti...

Background The construct of Essential Tremor plus (ET-plus) refers to patients who also have rest tremor and/or mild neurologic signs of unknown significance. It is unclear whether soft signs represent confounding factors or are useful in suspecting an alternative condition. Methods Using a Bayesian approach to ET-plus patients recruited in The IT...

Objectives: To test the hypothesis that the combined analysis of non-contrast CT (NCCT) and CT perfusion (CTP) imaging markers improves prediction of hematoma expansion (HE) and outcome in intracerebral hemorrhage (ICH). Methods: Retrospective, single-center analysis of patients with primary ICH undergoing NCCT and CTP within 6 h from onset. NCC...

Introduction The possibility to generalize our understandings on treatments and assessments to both familial frontotemporal dementia (f‐FTD) and sporadic FTD (s‐FTD) is a fundamental perspective for the near future, considering the constant advancement in potential disease‐modifying therapies that target particular genetic forms of FTD. We aimed to...

Background: Many single cases and small series of Guillain-Barré syndrome (GBS) associated with SARS-CoV-2 infection were reported during the COVID-19 outbreak worldwide. However, the debate regarding the possible role of infection in causing GBS is still ongoing. This multicenter study aimed to evaluate epidemiological and clinical findings of GB...

Background Recent research on animal models of ischemic stroke supports the idea that pharmacological treatment potentially enhancing intrinsic brain plasticity could modulate acute brain damage, with improved functional recovery. One of these new drugs is citicoline, which could provide neurovascular protection and repair effects. Objectives The...

Purpose Intracerebral hemorrhage (ICH) is an uncommon but deadly event in patients with COVID-19 and its imaging features remain poorly characterized. We aimed to describe the clinical and imaging features of COVID-19-associated ICH. Methods Multicenter, retrospective, case–control analysis comparing ICH in COVID-19 patients (COV19 +) versus contr...

Introduction: Previous studies reported increased plasma levels of Cystatin C (Cys-C) in Parkinson's disease (PD) and claimed for a possible association with disease severity and progression. The aim of this study was to evaluate plasma Cys-C in PD and healthy controls (HC) and test its association with markers of peripheral inflammation, neurodeg...

Objective Data on prognostic tools for indicating mechanical ventilation in older people with COVID-19 are still limited. The aim of this research was to evaluate if the multidimensional prognostic index (MPI), based on comprehensive geriatric assessment (CGA), may help physicians in identifying older hospitalized patients affected by COVID-19 who...

Toxic aggregates of α-synuclein (αsyn) are considered key drivers of Parkinson’s disease (PD) pathology. In early PD, αsyn induces synaptic dysfunction also modulating the glutamatergic neurotransmission. However, a more detailed understanding of the molecular mechanisms underlying αsyn-triggered synaptic failure is required to design novel therape...

Background: Sports-related concussion (SRC) is a subset of mild traumatic brain injuries occurring in contact sports. Most people recover spontaneously, but in retired professional players, the risk for neurodegenerative diseases is increased. A biomarker, such as neurofilament light chains (NfL), would help to address this issue and demonstrate s...

Objective: To assess whether non-invasive brain stimulation with transcranial alternating current stimulation at gamma-frequency (γ-tACS) applied over the precuneus can improve episodic memory and modulate cholinergic transmission by modulating cerebral rhythms in early Alzheimer's disease (AD). Methods: In this randomized, double-blind, sham co...

Introduction: The recently released classification has revised the nosology of tremor, defining essential tremor (ET) as a syndrome and fueling an enlightened debate about some newly conceptualized entities such as ET-plus. As a result, precise information of demographics, clinical features, and about the natural history of these conditions are la...

New diagnostic methods have been developed for the early diagnosis of Alzheimer’s disease (AD) with the primary purpose of intercepting the transition-phase (mild cognitive impairment, MCI) between normal aging and dementia. We aimed to explore whether the five-word test (FWT) and the mini-mental state examination (MMSE) are predictive for the earl...

Plasma phosphorylated tau species have been recently proposed as peripheral markers of Alzheimer’s disease (AD) pathology. In this cross-sectional study including 91 subjects, plasma and cerebrospinal fluid (CSF) p-tau181 and p-tau231 levels were elevated in the early symptomatic stages of AD. Plasma p-tau231 and p-tau181 were strongly related to C...

Recent studies suggest that COVID-19 survivors may experience long-term health consequences: in particular, neurological and mental health symptoms might be associated with long-term negative outcomes. This study is a secondary analysis of a larger cohort study and aims to determine the extent to which neurological and mental health sequelae are as...

Background: The assessment of human and diagnostic resources is a prerequisite to improving the management of emergency neurology. Objective: To provide a landscape on the organization of the Lombardy Region hospitals for emergency neurological care management. Methods: We designed an anonymized questionnaire including 6 sections with 21 quest...