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Exercise therapy in muscle diseases: open issues and future perspectives

Gabriele Siciliano, Erika Schirinzi, Costanza Simoncini, Giulia Ricci
2019 Acta myologica  
In muscle diseases different molecular mechanisms are responsible, by distinct cellular pathways, of muscle fibers contraction insufficiency and exercise intolerance. Depending on that, exercise therapy is a promising avenue to efficaciously counteract the loss of muscle fiber function or also the secondary effects due to the sedentary lifestyle as a consequence of the motor impairment. It has been debated whether or not muscle exercise is beneficial or harmful for patients with myopathic
more » ... ers, especially in some conditions as eccentric or maximal exercise. Several reports now suggest that supervised aerobic exercise training is safe and may be considered effective in improving oxidative capacity and muscle function in patients with various muscle disorders, including muscular dystrophies and metabolic myopathies, providing that it can be personalized and sized over the single patient capability. In doing that, advancement in outcomes measure recording and exercise delivery monitoring with comfortable investigation methods to assess muscle function and structure can be useful to detect the beneficial effects of a supervised motor training. Based on these considerations, but also especially considering the emerging new therapies in the field of neuromuscular disorders, exercise training can be included as part of the rehabilitation program for patients with a muscle disease, assumed it should be strictly supervised for its effects and to prevent involuntary muscle damage.
pmid:31970321 pmcid:PMC6955631 fatcat:lbpndumhzfd6bjsoyiihpw6e6q

Muscle exercise in limb girdle muscular dystrophies: pitfall and advantages

Gabriele Siciliano, Costanza Simoncini, Stefano Giannotti, Virna Zampa, Corrado Angelini, Giulia Ricci
2015 Acta myologica  
Different genetic mutations underlying distinct pathogenic mechanisms have been identified as cause of muscle fibers degeneration and strength loss in limb girdle muscular dystrophies (LGMD). As a consequence, exercise tolerance is affected in patients with LGMD, either as a direct consequence of the loss of muscle fibers or secondary to the sedentary lifestyle due to the motor impairment. It has been debated for many years whether or not muscle exercise is beneficial or harmful for patients
more » ... h myopathic disorders. In fact, muscular exercise would be considered in helping to hinder the loss of muscle tissue and strength. On the other hand, muscle structural defects in LGMD can result in instability of the sarcolemma, making it more likely to induce muscle damage as a consequence of intense muscle contraction, such as that performed during eccentric training. Several reports have suggested that supervised aerobic exercise training is safe and may be considered effective in improving oxidative capacity and muscle function in patients with LGMD, such as LGMD2I, LGMD2L, LGMD2A. More or less comfortable investigation methods applied to assess muscle function and structure can be useful to detect the beneficial effects of supervised training in LGMD. However, it is important to note that the available trials assessing muscle exercise in patients with LGMD have often involved a small number of patients, with a wide clinical heterogeneity and a different experimental design. Based on these considerations, resistance training can be considered part of the rehabilitation program for patients with a limb-girdle type of muscular dystrophy, but it should be strictly supervised to assess its effects and prevent possible development of muscle damage.
pmid:26155063 pmcid:PMC4478773 fatcat:yers6ohkhrcsrbrk47ctn3va24

Therapeutical Management and Drug Safety in Mitochondrial Diseases—Update 2020

Francesco Gruosso, Vincenzo Montano, Costanza Simoncini, Gabriele Siciliano, Michelangelo Mancuso
2020 Journal of Clinical Medicine  
Mitochondrial diseases (MDs) are a group of genetic disorders that may manifest with vast clinical heterogeneity in childhood or adulthood. These diseases are characterized by dysfunctional mitochondria and oxidative phosphorylation deficiency. Patients are usually treated with supportive and symptomatic therapies due to the absence of a specific disease-modifying therapy. Management of patients with MDs is based on different therapeutical strategies, particularly the early treatment of
more » ... ecific complications and the avoidance of catabolic stressors or toxic medication. In this review, we discuss the therapeutic management of MDs, supported by a revision of the literature, and provide an overview of the drugs that should be either avoided or carefully used both for the specific treatment of MDs and for the management of comorbidities these subjects may manifest. We finally discuss the latest therapies approved for the management of MDs and some ongoing clinical trials.
doi:10.3390/jcm10010094 pmid:33383961 fatcat:7lz227vzvzb4vdpgvtozisffmm

Mitochondrial ANT-1 related adPEO leading to cognitive impairment: is there a link?

Costanza Simoncini, Gabriele Siciliano, Gloria Tognoni, Michelangelo Mancuso
2017 Acta myologica  
ANT1 is one of the nuclear genes responsible of autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA multiple deletions. The course of ANT1- related adPEO is relatively benign, symptoms being generally restricted to skeletal muscle. Here we report the case of an Italian 74 years old woman with ANT1-related adPEO and dementia. Further studies are needed to assess the prevalence of central neurological manifestations in ANT1 mitochondrial disease.
pmid:28690391 pmcid:PMC5479106 fatcat:n5r5x3jjcjhudkldg576sodriu

Exercise-Related Oxidative Stress as Mechanism to Fight Physical Dysfunction in Neuromuscular Disorders

Gabriele Siciliano, Lucia Chico, Annalisa Lo Gerfo, Costanza Simoncini, Erika Schirinzi, Giulia Ricci
2020 Frontiers in Physiology  
Neuromuscular diseases (NMDs) are a group of often severely disabling disorders characterized by dysfunction in one of the main constituents of the motor unit, the cardinal anatomic-functional structure behind force and movement production. Irrespective of the different pathogenic mechanisms specifically underlying these disease conditions genetically determined or acquired, and the related molecular pathways involved in doing that, oxidative stress has often been shown to play a relevant role
more » ... ithin the chain of events that induce or at least modulate the clinical manifestations of these disorders. Due to such a putative relevance of the imbalance of redox status occurring in contractile machinery and/or its neural drive in NMDs, physical exercise appears as one of the most important conditions able to positively interfere along an ideal axis, going from a deranged metabolic cell homeostasis in motor unit components to the reduced motor performance profile exhibited by the patient in everyday life. If so, it comes out that it would be important to identify a proper training program, suitable for load and type of exercise that is able to improve motor performance in adaptation and response to such a homeostatic imbalance. This review therefore analyzes the role of different exercise trainings on oxidative stress mechanisms, both in healthy and in NMDs, also including preclinical studies, to elucidate at which extent these can be useful to counteract muscle impairment associated to the disease, with the final aim of improving physical functions and quality of life of NMD patients.
doi:10.3389/fphys.2020.00451 pmid:32508674 pmcid:PMC7251329 fatcat:6zgiwdjayzh2denvg464mzacs4

A multi-parametric protocol to study exercise intolerance in McArdle's disease

Giulia Ricci, Federica Bertolucci, Annalisa Logerfo, Costanza Simoncini, Riccardo Papi, Ferdinando Franzoni, Giacomo Dell'Osso, Adele Servadio, Maria Chiara Masoni, Gabriele Siciliano
2015 Acta myologica  
McArdle's disease is the most common metabolic myopathy of muscle carbohydrate metabolism, due to deficiency of myophosphorylase and alteration of glycogen breakdown in muscle. The clinical manifestations usually begin in young adulthood, with exercise intolerance, exercise-induced muscle cramps, pain and recurrent episodes of myoglobinuria. Many patients experience the second wind phenomenon, characterized by an improved tolerance for aerobic exercise approximately after eight minutes of motor
more » ... activity, secondary to the increased availability of blood glucose and free fatty acids associated to an enhanced glucose uptake by muscle cells. In this study, we aimed to test a multi-parametric protocol in order to detect the impairment of muscular metabolism and motor performance in patients with McArdle's disease. We enrolled 5 patients and 5 age-matched healthy subjects, that were evaluated by: (01) monitoring of physical activity with an electronic armband; (02) testing of cardiopulmonary, metabolic and respiratory responses to exercise with a cardiopulmonary exercise test and analyzing muscle fatigue during exercise test by surface electromyography (04) evaluating blood lactate and oxidative stress biomarkers at rest and during exercise. The patients were tested at baseline and after three days of carbohydrate-rich diet integrated with tricarboxylic acid cycle intermediate and creatine. The multiparametric protocol proved to be useful to detect the oxidative capacity impairment and the second wind phenomenon of patients. We did not observe any significant differences of muscle metabolic response during the exercise test after three days of carbohydrate-rich diet.
pmid:27199539 pmcid:PMC4859075 fatcat:4nldsnwu45aitnptzpqgyrwvzi

May "Mitochondrial Eve" and Mitochondrial Haplogroups Play a Role in Neurodegeneration and Alzheimer's Disease?

Elena Caldarazzo Ienco, Costanza Simoncini, Daniele Orsucci, Loredana Petrucci, Massimiliano Filosto, Michelangelo Mancuso, Gabriele Siciliano
2011 International Journal of Alzheimer's Disease  
Mitochondria, the powerhouse of the cell, play a critical role in several metabolic processes and apoptotic pathways. Multiple evidences suggest that mitochondria may be crucial in ageing-related neurodegenerative diseases. Moreover, mitochondrial haplogroups have been linked to multiple area of medicine, from normal ageing to diseases, including neurodegeneration. Polymorphisms within the mitochondrial genome might lead to impaired energy generation and to increased amount of reactive oxygen
more » ... ecies, having either susceptibility or protective role in several diseases. Here, we highlight the role of the mitochondrial haplogroups in the pathogenetic cascade leading to diseases, with special attention to Alzheimer's disease.
doi:10.4061/2011/709061 pmid:21423558 pmcid:PMC3056451 fatcat:v25x6hofargshjmucmnqm35ko4

Central Nervous System Involvement as Outcome Measure for Clinical Trials Efficacy in Myotonic Dystrophy Type 1

Costanza Simoncini, Giulia Spadoni, Elisa Lai, Lorenza Santoni, Corrado Angelini, Giulia Ricci, Gabriele Siciliano
2020 Frontiers in Neurology  
Increasing evidences indicate that in Myotonic Dystrophy type 1 (DM1 or Steinert disease), an autosomal dominant multisystem disorder caused by a (CTG)n expansion in DMPK gene on chromosome 19q13. 3, is the most common form of inherited muscular dystrophy in adult patients with a global prevalence of 1/8000, and involvement of the central nervous system can be included within the core clinical manifestations of the disease. Variable in its severity and progression rate over time, likely due to
more » ... he underlying causative molecular mechanisms; this component of the clinical picture presents with high heterogeneity involving cognitive and behavioral alterations, but also sensory-motor neural integration, and in any case, significantly contributing to the disease burden projected to either specific functional neuropsychological domains or quality of life as a whole. Principle manifestations include alterations of the frontal lobe function, which is more prominent in patients with an early onset, such as in congenital and childhood onset forms, here associated with severe intellectual disabilities, speech and language delay and reduced IQ-values, while in adult onset DM1 cognitive and neuropsychological findings are usually not so severe. Different methods to assess central nervous system involvement in DM1 have then recently been developed, these ranging from more classical psychometric and cognitive functional instruments to sophisticated psycophysic, neurophysiologic and especially computerized neuroimaging techniques, in order to better characterize this disease component, at the same time underlining the opportunity to consider it a suitable marker on which measuring putative effectiveness of therapeutic interventions. This is the reason why, as outlined in the conclusive section of this review, the Authors are lead to wonder, perhaps in a provocative and even paradoxical way to arise the question, whether or not the myologist, by now the popular figure in charge to care of a patient with the DM1, needs to remain himself a neurologist to better appreciate, evaluate and speculate on this important aspect of Steinert disease.
doi:10.3389/fneur.2020.00624 pmid:33117249 pmcid:PMC7575726 fatcat:hrstjh3jdbeublr7ildtmo6k2i

Relationship between neuropsychological impairment and grey and white matter changes in adult-onset myotonic dystrophy type 1

Sigrid Baldanzi, Paolo Cecchi, Serena Fabbri, Ilaria Pesaresi, Costanza Simoncini, Corrado Angelini, Ubaldo Bonuccelli, Mirco Cosottini, Gabriele Siciliano
2016 NeuroImage: Clinical  
Myotonic dystrophy type 1 (DM1) has a wide phenotypic spectrum and potentially may affect central nervous system with mild to severe involvement. Our aim was to investigate grey matter (GM) and white matter (WM) structural alterations in a sample of adult-onset DM1 patients and to evaluate relationship with clinical and cognitive variables. Thirty DM1 patients underwent neuropsychological investigation and 3T-MRI protocol. GM and WM changes were evaluated calculating brain parenchymal fraction
more » ... BPF), voxel-based morphometry (VBM), white matter lesion load (LL% and Fazekas scale) and tract based spatial statistical (TBSS). Patients showed main impairment in tests exploring executive and mnesic domains with visuo-spatial involvement, significantly related to BPF. VBM revealed clusters of widespread GM reduction and TBSS revealed areas of decreased fractional anisotropy (FA) and increased radial diffusivity (RD), mean diffusivity (MD) and axial diffusivity (AD) in patients compared to a group of matched healthy controls. Multiple regression analyses showed areas of significant negative relationship between left temporal atrophy and verbal memory, between RD and mnesic and visuo-spatial cognitive domains, and between AD and verbal memory. TBSS results indicate that the involvement of normal appearance WM, beyond the signal changes detected with conventional MR imaging (Fazekas scale and LL%), was associated with neuropsychological deficit. These data suggest that disrupted complex neuronal networks can underlie cognitive-behavioural dysfunctions in DM1.
doi:10.1016/j.nicl.2016.06.011 pmid:27437180 pmcid:PMC4939389 fatcat:njbo6mtgxbcetj7q25rag7mdp4

Disease awareness in myotonic dystrophy type 1: an observational cross-sectional study

Sigrid Baldanzi, Francesca Bevilacqua, Rita Lorio, Leda Volpi, Costanza Simoncini, Antonio Petrucci, Mirco Cosottini, Gabriele Massimetti, Gloria Tognoni, Giulia Ricci, Corrado Angelini, Gabriele Siciliano
2016 Orphanet Journal of Rare Diseases  
Myotonic dystrophy type 1 (Steinert's disease or DM1), the most common form of autosomal dominant muscular dystrophy in adults, is a multisystem disorder, affecting skeletal muscle as well as eyes, heart, gastrointestinal tract, endocrine system, and central nervous system, finally responsible of increasing disabilities and secondary social consequences. To date, DM1-related brain involvement represents a challenging field of research. It is well known that DM1 patients frequently present
more » ... sychological disturbances and psychiatric comorbidities among which reduced awareness of disease burden and its progression, also defined as anosognosia, is common in clinical practice, this leading to secondary misattribution of symptoms, delay in timely diagnostic procedures and low compliance to treatment. Methods: Here we present an observational cross sectional study in which disease-related cognitive dysfunctions and quality of life were assessed by a protocol finally designed to estimate the prevalence of disease awareness in a sample of 65 adult-onset DM1 patients. Results: Our analysis showed that in DM1 patients several cognitive functions, including executive and mnesic domains with visuo-spatial involvement, were affected. The assessment of anosognosia revealed that a high percentage (51.6 %) of DM1 subjects was disease unaware. The reduced illness awareness occurs across different physical and life domains, and it appears more prominent in Activities and Independence domains investigated by the Individualized Neuromuscular Quality Of Life (INQoL) questionnaire. Moreover, the unawareness resulted significantly related (at p <0.05 and p < 0.01) to the performance failure in cognitive tests, specifically in the domains of visuo-spatial memory, cognitive flexibility and conceptualization. Conclusions: The obtained data confirm, by a systematic analysis, what's the common clinical perceiving of disease unawareness in Steinert's disease, this related to the already known cognitive-behavioural impairment of frontal type in affected patients. We believe that a deep knowledge of this aspect will be useful for medical practice in the management of patients with DM1, also for guidance in occupational and social interventions, definition of outcome measures and in preparation of trial readiness.
doi:10.1186/s13023-016-0417-z pmid:27044540 pmcid:PMC4820880 fatcat:5ohvqil5mveahif6bjm7s43cne

Towards a patient-specific hepatic arterial modeling for microspheres distribution optimization in SIRT protocol

Costanza Simoncini, Krzysztof Jurczuk, Daniel Reska, Simon Esneault, Jean-Claude Nunes, Jean-Jacques Bellanger, Hervé Saint-Jalmes, Yan Rolland, Pierre-Antoine Eliat, Johanne Bézy-Wendling, Marek Kretowski
2017 Medical and Biological Engineering and Computing  
Selective Internal Radiation Therapy (SIRT) using Yttrium-90 loaded glass microspheres injected in the hepatic artery is an emerging, minimally invasive therapy of liver cancer. A personalized intervention can lead to high concentration dose in the tumor, while sparing the surrounding parenchyma. We propose a computational model for patient-specific simulation of entire hepatic arterial tree, based on liver, tumors and arteries segmentation on patient's tomography. Segmentation of hepatic
more » ... es down to a diameter of 0.5 mm is semi-automatically performed on 3D Cone-Beam CT Angiography. Liver and tumors are extracted from CT-scan at portal phase by an active surface method. Once the images are registered through an automatic multimodal registration, extracted data are used to initialize a numerical model simulating liver vascular net-work. The model creates successive bifurcations from given principal vessels, observing Poiseuille's and matter conservation laws. Simulations provide a coherent reconstruction of global hepatic arterial tree until vessel diameter of 0.05 mm. Microspheres distribution under simple hypotheses is also quantified, depending on injection site. The patient-specific character of this model may allow a personalized numerical approximation of microspheres final distribution, opening the way to clinical optimization of catheter placement for tumor targeting.
doi:10.1007/s11517-017-1703-1 pmid:28825200 fatcat:svgjgiqqpneurlfvwi4eaaujpe

Movement Disorders in Children with a Mitochondrial Disease: A Cross-Sectional Survey from the Nationwide Italian Collaborative Network of Mitochondrial Diseases

Chiara Ticci, Daniele Orsucci, Anna Ardissone, Luca Bello, Enrico Bertini, Irene Bonato, Claudio Bruno, Valerio Carelli, Daria Diodato, Stefano Doccini, Maria Alice Donati, Claudia Dosi (+29 others)
2021 Journal of Clinical Medicine  
Movement disorders are increasingly being recognized as a manifestation of childhood-onset mitochondrial diseases (MDs). However, the spectrum and characteristics of these conditions have not been studied in detail in the context of a well-defined cohort of patients. We retrospectively explored a cohort of individuals with childhood-onset MDs querying the Nationwide Italian Collaborative Network of Mitochondrial Diseases database. Using a customized online questionnaire, we attempted to collect
more » ... data from the subgroup of patients with movement disorders. Complete information was available for 102 patients. Movement disorder was the presenting feature of MD in 45 individuals, with a mean age at onset of 11 years. Ataxia was the most common movement disorder at onset, followed by dystonia, tremor, hypokinetic disorders, chorea, and myoclonus. During the disease course, most patients (67.7%) encountered a worsening of their movement disorder. Basal ganglia involvement, cerebral white matter changes, and cerebellar atrophy were the most commonly associated neuroradiological patterns. Forty-one patients harbored point mutations in the mitochondrial DNA, 10 carried mitochondrial DNA rearrangements, and 41 cases presented mutations in nuclear-DNA-encoded genes, the latter being associated with an earlier onset and a higher impairment in activities of daily living. Among our patients, 32 individuals received pharmacological treatment; clonazepam and oral baclofen were the most commonly used drugs, whereas levodopa and intrathecal baclofen administration were the most effective. A better delineation of the movement disorders phenotypes starting in childhood may improve our diagnostic workup in MDs, fine tuning management, and treatment of affected patients.
doi:10.3390/jcm10102063 pmid:34065803 fatcat:rqfhznxz6zdkxh4kxrubffxhi4

NEWS and VIEWS: mitochondrial encephalomyopathies

Elena Caldarazzo Ienco, Daniele Orsucci, Vincenzo Montano, Elena Ferrari, Lucia Petrozzi, Marta Cheli, Annalisa Logerfo, Costanza Simoncini, Gabriele Siciliano, Michelangelo Mancuso
2016 unpublished
In recent years, there has been a surge of interest in mitochon-drial diseases, a group of metabolic conditions caused by impairment of the oxidative phosphorylation system. The ubiquitous presence of mitochondria in all the cells of the body, their role as cell powerhouse and their particular genetic characteristics explain the phenotypic complexity and the diagnostic difficulties , bridging from paediatrician to neurologist.
fatcat:ublx5iapmrdz7o5t4ekus7bazu

Muscle exercise in limb girdle muscular dystrophies: pitfall and advantages

Gabriele Siciliano, Costanza Simoncini, Stefano Giannotti, Virna Zampa, Corrado Angelini, Giulia Ricci
2015 unpublished
Different genetic mutations underlying distinct pathogenic mechanisms have been identified as cause of muscle fibers de-generation and strength loss in limb girdle muscular dystro-phies (LGMD). As a consequence, exercise tolerance is affected in patients with LGMD, either as a direct consequence of the loss of muscle fibers or secondary to the sedentary lifestyle due to the motor impairment. It has been debated for many years whether or not muscle exercise is beneficial or harmful for patients
more » ... ith myopathic disorders. In fact, muscular exercise would be considered in helping to hinder the loss of muscle tissue and strength. On the other hand, muscle structural defects in LGMD can result in instability of the sarcolemma, making it more likely to induce muscle damage as a consequence of intense muscle contraction, such as that performed during eccentric training. Several reports have suggested that supervised aerobic exercise training is safe and may be considered effective in improving oxidative capacity and muscle function in patients with LGMD, such as LGMD2I, LGMD2L, LGMD2A. More or less comfortable investigation methods applied to assess muscle function and structure can be useful to detect the beneficial effects of supervised training in LGMD. However, it is important to note that the available trials assessing muscle exercise in patients with LGMD have often involved a small number of patients, with a wide clinical het-erogeneity and a different experimental design. Based on these considerations, resistance training can be considered part of the rehabilitation program for patients with a limb-girdle type of muscular dystrophy, but it should be strictly supervised to assess its effects and prevent possible development of muscle damage.
fatcat:znknrycabjd77o23emfzx3i7di

Hard ways towards adulthood: the transition phase in young people with myotonic dystrophy

Sigrid Baldanzi, Giulia Ricci, Costanza Simoncini, Mirna Cosci, Di Coscio, Gabriele Siciliano, Sigrid Baldanzi
2016 Acta Myologica •   unpublished
Myotonic dystrophy type 1 (DM1), also called Steinert's disease, is a genetic multisystem disorder that has raised, in the last years, high interest because of the high variable clinical spectrum and related disability. Children with myotonic dystrophy are affected by behavioural problems and intellectual disability , finally impacting on their degree of engagement in family, work and social activities. The transition phase, representing the process of moving from adolescence to adulthood, can
more » ... e severely affected by growing up with a neuromuscular disorder, with significant impact on patient's and families' quality of life. Although conceptual models of health assistance for individual with genetic disorders have already been proposed the burden for the patient and his family is still relevant. Therefore to afford this critical condition it would be suitable to plan proper educational and psychosocial programs, identifying areas of un-met needs and targeted health objectives that ensure the right support to DM1 population.
fatcat:tg5cisv7fjegbn4vc3uo5tyvie
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