Luca magistrelli
@uninsubria.it
University of Insubria
Scopus Publications
Scopus Publications
Filomena Abate, Francesca Di Biasio, Roberta Marchese, Tiziana Benzi Markushi, Andrea Ciammola, Nicola Ticozzi, Giovanna Calandra-Buonaura, Ilaria Cani, Luisa Sambati, Giovanni Fabbrini,et al.
Elsevier BV
Valentina Ciampana, Lucia Corrado, Luca Magistrelli, Elena Contaldi, Cristoforo Comi, Sandra D’Alfonso, and Domizia Vecchio
MDPI AG
Background/Objectives: Axonal Charcot–Marie–Tooth disease type 2 (CMT2) accounts for 24% of Hereditary Motor/Sensory Peripheral Neuropathies. CMT2 type GG, due to four distinct heterozygous mutations in the Golgi brefeldin A resistant guanine nucleotide exchange factor 1 (GBF1) gene (OMIM 606483), was described in seven cases from four unrelated families with autosomal dominant inheritance. It is characterized by slowly progressive distal muscle weakness and atrophy, primarily affecting the lower limbs. Here, we present two siblings sharing a novel GBF1 variant. Methods: Patient II.1 (male, 61 years at onset) presented lower limb hypoesthesia and walking difficulty; the examination revealed a postural tremor, a positive Romberg test, and muscle atrophy in the lower limbs and hands. Patient II.2 (his sister, 59 years at onset) had lower limb dysesthesias, hand paresthesia, and lower-limb stiffness. They underwent clinical evaluations, blood tests, and electroneurography. Their father represents a potentially affected individual, although a genetic analysis was not conducted. Results: All tests for peripheral neuropathies were unremarkable, including metabolic and autoimmune screening. Both showed a mixed demyelinating–axonal sensory–motor neuropathy. Genetic analysis revealed a new heterozygous GBF1 variant of uncertain significance. Conclusions: Based on autosomal dominant inheritance, as well as clinical and physiological features, a possible novel CMT2GG was diagnosed. Further research, including functional assays and in vitro studies, is necessary to confirm this variant’s causal link.
Arianna Cappiello, Paolo Barone, Marina Picillo, and
Wiley
Luca Magistrelli, Elena Contaldi, Annalisa Visciglia, Giovanni Deusebio, Marco Pane, and Angela Amoruso
MDPI AG
Introduction. Previous studies have shown that probiotics have positive effects on both motor and non-motor symptoms in Parkinson’s disease (PD). Additionally, in preclinical settings, probiotics have demonstrated the ability to counteract neuronal loss and alpha-synuclein aggregation, important pathological hallmarks of PD. Notably, preliminary in vitro studies have revealed the immunomodulatory properties of probiotics. This study aims to evaluate the impact of probiotics on symptoms and peripheral cytokines levels in PD patients compared to placebo. Methods. Patients were enrolled and blindly randomized to receive either active probiotics (comprising Bifidobacterium animalis subsp. lactis BS01 LMG P-21384, Bifidobacterium longum BL03 DSM 16603, Bifidobacterium adolescentis BA02 DSM 18351, Fructo-oligosaccharides and Maltodextrin-Group A) or placebo (Maltodextrin-Group B). Clinical evaluations and plasma levels cytokines (TNF-α, IFN-γ, IL-6, and TGF-β) were also assessed at enrollment and after 12 weeks. Anti-parkinsonian therapy remained stable throughout the study. Results. Forty PD patients were recruited. After 12 weeks, Group A showed significant improvement in motor symptoms (UPDRS III: 13.89 ± 4.08 vs. 12.74 ± 4.57, p = 0.028) and non-motor symptoms (NMSS: 34.32 ± 21.41 vs. 30.11 ± 19.89, p = 0.041), with notable improvement in the gastrointestinal sub-item (3.79 ± 4.14 vs. 1.89 ± 2.54, p = 0.021). A reduction of IFN-γ levels was observed in both groups, but group A also showed a significant decrease in IL-6 and a slight increase in the anti-inflammatory cytokine TGF-β. Conclusions. Our data suggest that probiotics may modulate peripheral cytokines levels and improve clinical symptoms in PD patients. Probiotics may, therefore, represent a valuable adjunctive therapy to conventional anti-parkinsonian drugs.
Federica Arienti, Giovanni Casazza, Giulia Franco, Giulia Lazzeri, Edoardo Monfrini, Alessandro Di Maio, Roberto Erro, Paolo Barone, Filippo Tamma, Elena Caputo,et al.
Wiley
AbstractBackgroundFamily history of Parkinson's disease (PD) is a common finding in PD patients. However, a few studies have systematically examined this aspect.ObjectivesWe investigated the family history of PD patients, comparing demographic and clinical features between familial PD (fPD) and sporadic PD (sPD).MethodsA cross‐sectional study enrolling 2035 PD patients was conducted in 28 Italian centers. Clinical data and family history up to the third degree of kinship were collected.ResultsFamily history of PD was determined in 21.9% of patients. fPD patients had earlier age at onset than sporadic patients. No relevant differences in the prevalence of motor and nonmotor symptoms were detected. Family history of mood disorders resulted more prevalently in the fPD group.ConclusionsfPD was found to recur more frequently than previously reported. Family history collection beyond the core family is essential to discover disease clusters and identify novel risk factors for PD.
Margherita Fabbri, Claudia Ledda, Tommaso Schirinzi, Carlo Alberto Artusi, Anna Rosa Avallone, Henri Zenuni, Rosa De Micco, Simone Aloisio, Ilaria Cani, Maria Chiara Malaguti,et al.
Elsevier BV
Luca Magistrelli, Elena Contaldi, Beatrice Piola, Fjorilda Caushi, Miryam Carecchio, Sandra D'Alfonso, and Lucia Corrado
Wiley
Vittorio Velucci, Sarah Idrissi, Roberta Pellicciari, Marcello Esposito, Assunta Trinchillo, Daniele Belvisi, Giovanni Fabbrini, Gina Ferrazzano, Carmen Terranova, Paolo Girlanda,et al.
BMJ
BackgroundSeveral earlier studies showed a female predominance in idiopathic adult-onset dystonia (IAOD) affecting the craniocervical area and a male preponderance in limb dystonia. However, sex-related differences may result from bias inherent to study design. Moreover, information is lacking on whether sex-related differences exist in expressing other dystonia-associated features and dystonia spread.ObjectiveTo provide accurate information on the relationship between sex differences, motor phenomenology, dystonia-associated features and the natural history of IAOD.MethodsData of 1701 patients with IAOD from the Italian Dystonia Registry were analysed.ResultsWomen predominated over men in blepharospasm, oromandibular, laryngeal and cervical dystonia; the sex ratio was reversed in task-specific upper limb dystonia; and no clear sex difference emerged in non-task-specific upper limb dystonia and lower limb dystonia. This pattern was present at disease onset and the last examination. Women and men did not significantly differ for several dystonia-associated features and tendency to spread. In women and men, the absolute number of individuals who developed dystonia tended to increase from 20 to 60 years and then declined. However, when we stratified by site of dystonia onset, different patterns of female-to-male ratio over time could be observed in the various forms of dystonia.ConclusionsOur findings provide novel evidence on sex as a key mediator of IAOD phenotype at disease onset. Age-related sexual dimorphism may result from the varying exposures to specific age-related and sex-related environmental risk factors interacting in a complex manner with biological factors such as hormonal sex factors.
Roberto Erro, Giulia Lazzeri, Carmen Terranova, Giulia Paparella, Angelo Fabio Gigante, Rosa De Micco, Luca Magistrelli, Francesca Di Biasio, Francesca Valentino, Vincenzo Moschella,et al.
Wiley
AbstractBackgroundTremor disorders remain as clinical diagnoses and the rate of misdiagnosis between the commonest non‐parkinsonian tremors is relatively high.ObjectivesTo compare the clinical features of Essential Tremor without other features (pure ET), ET plus soft dystonic signs (ET + DS), and tremor combined with dystonia (TwD).MethodsWe compared the clinical features of patients with pure ET, ET + DS, and TwD enrolled in The ITAlian tremor Network (TITAN). Linear regression models were performed to determine factors associated with health status and quality of life.ResultsThree‐hundred‐eighty‐three patients were included. Sex distribution was significantly different between the groups with males being more represented in pure ET and females in TwD. The initial site of tremor was different between the groups with about 40% of TwD having head tremor and ET + DS unilateral upper limb tremor at onset. This pattern mirrored the distribution of overt dystonia and soft dystonic signs at examination. Sensory trick, task‐specificity, and position‐dependence were more common, but not exclusive, to TwD. Pure ET patients showed the lowest degree of alcohol responsiveness and ET + DS the highest. Midline tremor was more commonly encountered and more severe in TwD than in the other groups. Regression analyses demonstrated that tremor severity, sex, age, and to a lesser degree the variable “group”, independently predicted health status and quality of life, suggesting the existence of other determinants beyond tremor.ConclusionsPure ET and TwD manifest with a phenotypic overlap, which calls for the identification of diagnostic biomarkers. ET + DS shared features with both syndromes, suggesting intra‐group heterogeneity.
Elena Contaldi, Silvia Gallo, Lucia Corrado, Sandra D’Alfonso, and Luca Magistrelli
Springer Science and Business Media LLC
Sarah Idrissi, Vittorio Velucci, Marcello Esposito, Assunta Trinchillo, Francesco Habestwallner, Daniele Belvisi, Giovanni Fabbrini, Gina Ferrazzano, Vincenzo Rizzo, Carmen Terranova,et al.
Springer Science and Business Media LLC
Luca Magistrelli, Elena Contaldi, Sandra D'Alfonso, and Lucia Corrado
Wiley
Silvia Gallo, Francesca Vignaroli, Elena Contaldi, Domizia Vecchio, Lucia Corrado, Sandra D'Alfonso, Roberto Cantello, and Luca Magistrelli
Elsevier BV
Elena Contaldi, Gaetano Leogrande, Riccardo Fornaro, Cristoforo Comi, and Luca Magistrelli
Wiley
Luca Magistrelli, Elena Contaldi, Fjorilda Caushi, Alice Spano, Roberto Cantello, Sandra D’Alfonso, and Lucia Corrado
Springer Science and Business Media LLC
Stefano Martini, Franca Marino, Luca Magistrelli, Elena Contaldi, Marco Cosentino, and Cristoforo Comi
Springer Science and Business Media LLC
Abstract Background Parkinson’s disease (PD) is a common neurodegenerative disease. No disease-modifying treatment is available, and therapy is symptomatic. The histopathologic hallmark is the loss of dopaminergic neurons and accumulation of α-synuclein (α-syn) in surviving neurons, but the underlying pathophysiology is unclear. Inflammatory mechanisms seem to play a prominent role, with an imbalance of immune functions and neurotoxicity caused by reactive oxygen species (ROS). Involvement of peripheral adaptive immunity, with an imbalance in T cell subpopulations and in the expression of transcriptional factors in CD4+ T cells, has also been reported. Although clinical presentation is defined by motor symptoms, patients also report non-motor symptoms, often before the onset of a clinically established disease. Etiopathogenesis of PD is unknown, but an initial aggregation of α-syn in the gut, with subsequent propagation along the vagus nerve to the brain has been hypothesised. Interestingly, in an α-syn overexpressing murine model, the absence of gut microbiota prevented both microglia activation and motor impairment, thus pointing to a fundamental role of microbiota in the development of PD. Magistrelli et al. showed that in peripheral blood mononuclear cells of PD patients, probiotics modulate the in vitro production of cytokines toward an anti-inflammatory profile and reduce the production of ROS. Methods This is a pilot randomised placebo-controlled clinical trial protocol for a 12-week treatment with probiotics. At least 80 patients affected by PD will be recruited and randomly allocated to either the treatment or placebo group in a 1:1 ratio. General inclusion criteria will be the onset of PD 2 to 5 years before the trial and absence of autoimmune comorbidities or immunomodulating therapy. Our primary endpoint is the assessment of changes in extracellular cytokine levels (Interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-4, and IL-10) and ROS production. Secondary outcomes include changes in lymphocyte subpopulations and transcriptional factors mRNA levels. Discussion This study is designed to highlight the potential beneficial role of probiotics administration on peripheral immunity through the modulation of gut microbiota. Explorative outcomes will be evaluated to assess variations in motor and non-motor symptoms and the possible correlation with probiotics administration. Trial registration ClinicalTrials.gov ID NCT05173701. Registered 08 November 2021
Marcello Mario Mascia, Daniele Belvisi, Marcello Esposito, Roberta Pellicciari, Assunta Trinchillo, Carmen Terranova, Salvatore Bertino, Laura Avanzino, Francesca Di Biasio, Francesco Bono,et al.
Elsevier BV
Massimo Canonico, Francesco Desimoni, Alberto Ferrero, Pietro Antonio Grassi, Christopher Irwin, Daiana Campani, Alberto Dal Molin, Massimiliano Panella, and Luca Magistrelli
MDPI AG
Gait abnormalities are common in the elderly and individuals diagnosed with Parkinson’s, often leading to reduced mobility and increased fall risk. Monitoring and assessing gait patterns in these populations play a crucial role in understanding disease progression, early detection of motor impairments, and developing personalized rehabilitation strategies. In particular, by identifying gait irregularities at an early stage, healthcare professionals can implement timely interventions and personalized therapeutic approaches, potentially delaying the onset of severe motor symptoms and improving overall patient outcomes. In this paper, we studied older adults affected by chronic diseases and/or Parkinson’s disease by monitoring their gait due to wearable devices that can accurately detect a person’s movements. In our study, about 50 people were involved in the trial (20 with Parkinson’s disease and 30 people with chronic diseases) who have worn our device for at least 6 months. During the experimentation, each device collected 25 samples from the accelerometer sensor for each second. By analyzing those data, we propose a metric for the “gait quality” based on the measure of entropy obtained by applying the Fourier transform.
Giovanni Defazio, Angelo Fabio Gigante, Roberto Erro, Daniele Belvisi, Marcello Esposito, Assunta Trinchillo, Gabriella De Joanna, Roberto Ceravolo, Sonia Mazzucchi, Elisa Unti,et al.
Wiley
Elena Contaldi, Luca Magistrelli, Alessia Furgiuele, Silvia Gallo, and Cristoforo Comi
Springer Science and Business Media LLC
Roberto Cilia, Emanuele Cereda, Marco Piatti, Andrea Pilotto, Luca Magistrelli, Nico Golfrè Andreasi, Salvatore Bonvegna, Elena Contaldi, Francesca Mancini, Gabriele Imbalzano,et al.
Wiley
Roberto Erro, Giulia Lazzeri, Angelo Fabio Gigante, Andrea Pilotto, Luca Magistrelli, Matteo Bologna, Carmen Terranova, Enrica Olivola, Carlo Dallocchio, Vincenzo Moschella,et al.
Frontiers Media SA
BackgroundTo date, there are no large studies delineating the clinical correlates of “pure” essential tremor (ET) according to its new definition.MethodsFrom 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, and task-specific tremor, which were formerly considered parts of the ET spectrum.ResultsOut of 653 subjects recruited in the TITAN study by January 2022, the data of 208 (31.8%) “pure” ET patients (86M/122F) were analyzed. The distribution of age at onset was found to be bimodal. The proportion of familial cases by the age-at-onset class of 20 years showed significant differences, with sporadic cases representing the large majority of the class with an age at onset above 60 years. Patients with a positive family history of tremor had a younger onset and were more likely to have leg involvement than sporadic patients despite a similar disease duration. Early-onset and late-onset cases were different in terms of tremor distribution at onset and tremor severity, likely as a function of longer disease duration, yet without differences in terms of quality of life, which suggests a relatively benign progression. Treatment patterns and outcomes revealed that up to 40% of the sample was unsatisfied with the current pharmacological options.DiscussionThe findings reported in the study provide new insights, especially with regard to a possible inversed sex distribution, and to the genetic backgrounds of “pure” ET, given that familial cases were evenly distributed across age-at-onset classes of 20 years. Deep clinical profiling of “pure” ET, for instance, according to age at onset, might increase the clinical value of this syndrome in identifying pathogenetic hypotheses and therapeutic strategies.
Elena Contaldi, Luca Magistrelli, and Cristoforo Comi
Elsevier
Cristoforo Comi, Luca Magistrelli, and Elena Contaldi
Bentham Science Publishers Ltd.
Abstract: Parkinson’s disease (PD) is a common neurodegenerative disease characterized by loss of dopaminergic neurons and intraneuronal accumulation of protein aggregates. The exact mechanisms leading to neuronal death in PD are not fully understood, but several different molecular pathways are involved, leading to the concept that molecular subtypes may coexist in the nosological spectrum of PD. To this respect, immune system activation, both in the periphery and inside the central nervous system, was detected as a common trait of several pathogenic pathways of PD. The current working hypothesis implies that immune cells shift towards a proinflammatory phenotype and trigger the production of neurotoxic cytokines, ultimately contributing to neurodegeneration. While it is very important to understand how commonly used antiparkinson drugs interact with such changes, the search for treatments which may directly or indirectly modulate immune function is a great opportunity for disease modification.
Carlo Alberto Artusi, Elisa Montanaro, Roberto Erro, Nils Margraf, Christian Geroin, Andrea Pilotto, Luca Magistrelli, Francesca Spagnolo, Alberto Marchet, Lidia Sarro,et al.
Wiley