114 results on '"Mancuso, Michelangelo"'
Search Results
52. The mtDNA A8344G “MERRF” mutation is not a common cause of sporadic Parkinson disease in Italian population
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Mancuso, Michelangelo, Nesti, Claudia, Petrozzi, Lucia, Orsucci, Daniele, Frosini, Daniela, Kiferle, Lorenzo, Bonuccelli, Ubaldo, Ceravolo, Roberto, Murri, Luigi, and Siciliano, Gabriele
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- 2008
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53. Letter to the editor P301L Tau mutation and non-Alzheimer dementias in Italy.
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Mancuso, Michelangelo, Leone, Maria, Filosto, Massimiliano, Tognoni, Gloria, Siciliano, Gabriele, Nichelli, Paolo, and Murri, Luigi
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GENETIC mutation , *GENES , *DEMENTIA , *PARALYSIS , *DEGENERATION (Pathology) , *RESEARCH - Abstract
Focuses on the breakthrough in medical science research which reveals that mutations in the tau gene are responsible for familial fronto-temporal dementia (FTD), progressive supranuclear palsy (PSP) and cortico-basal degeneration (CBD). Revelation that Proline-to-Leucine mutation at codon 301 is the most common tau mutation in FTD; Details of the study conducted in Italy to assess the frequency of Proline-to-Leucine mutation; Information on the type of patients selected for the study.
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- 2003
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54. Frontotemporal Dementia, Where Do We Stand? A Narrative Review.
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Antonioni, Annibale, Raho, Emanuela Maria, Lopriore, Piervito, Pace, Antonia Pia, Latino, Raffaela Rita, Assogna, Martina, Mancuso, Michelangelo, Gragnaniello, Daniela, Granieri, Enrico, Pugliatti, Maura, Di Lorenzo, Francesco, and Koch, Giacomo
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FRONTOTEMPORAL dementia , *LARGE-scale brain networks , *BRAIN stimulation , *SYMPTOMS , *MOTOR neuron diseases , *TEMPORAL lobe , *AMYOTROPHIC lateral sclerosis - Abstract
Frontotemporal dementia (FTD) is a neurodegenerative disease of growing interest, since it accounts for up to 10% of middle-age-onset dementias and entails a social, economic, and emotional burden for the patients and caregivers. It is characterised by a (at least initially) selective degeneration of the frontal and/or temporal lobe, generally leading to behavioural alterations, speech disorders, and psychiatric symptoms. Despite the recent advances, given its extreme heterogeneity, an overview that can bring together all the data currently available is still lacking. Here, we aim to provide a state of the art on the pathogenesis of this disease, starting with established findings and integrating them with more recent ones. In particular, advances in the genetics field will be examined, assessing them in relation to both the clinical manifestations and histopathological findings, as well as considering the link with other diseases, such as amyotrophic lateral sclerosis (ALS). Furthermore, the current diagnostic criteria will be explored, including neuroimaging methods, nuclear medicine investigations, and biomarkers on biological fluids. Of note, the promising information provided by neurophysiological investigations, i.e., electroencephalography and non-invasive brain stimulation techniques, concerning the alterations in brain networks and neurotransmitter systems will be reviewed. Finally, current and experimental therapies will be considered. [ABSTRACT FROM AUTHOR]
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- 2023
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55. Intravenous thrombolysis + endovascular thrombectomy versus thrombolysis alone in large vessel occlusion mild stroke: a propensity score matched analysis.
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Schwarz, Ghil, Bonato, Sara, Lanfranconi, Silvia, Matusevicius, Marius, Ghione, Isabella, Valcamonica, Gloria, Tsivgoulis, Georgios, Paiva Nunes, Ana, Mancuso, Michelangelo, Zini, Andrea, Candelaresi, Paolo, Rand, Viiu‐Marika, Comi, Giacomo P., Mazya, Michael V., and Ahmed, Niaz
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ENDOVASCULAR surgery , *PROPENSITY score matching , *STROKE , *INTERNAL carotid artery , *THROMBOLYTIC therapy , *LACUNAR stroke - Abstract
Background and purpose: The best reperfusion treatment for patients with mild acute ischaemic stroke harbouring proximal anterior circulation large vessel occlusion (LVO) is unknown. The aim was to compare the safety and efficacy of intravenous thrombolysis (IVT) plus endovascular thrombectomy (EVT) versus IVT alone in LVO patients with mild symptoms. Methods: From the Safe Implementation of Treatment in Stroke–International Stroke Thrombolysis and Thrombectomy Register (SITS‐ISTR), were included: (i) consecutive acute ischaemic stroke patients, (ii) treated within 4.5 h from symptoms onset, (iii) baseline National Institutes of Health Stroke Scale (NIHSS) score ≤5 and (iv) intracranial internal carotid artery [ICA], M1 or T occlusion [defined as occlusion of ICA terminal bifurcation]. After propensity score matching, 3‐month functional outcomes (modified Rankin Scale [mRS] 0–1 and 0–2) and safety outcomes (symptomatic intracerebral haemorrhage and death) were compared (via univariable and multivariable logistic [and ordinal] regression analyses) in patients treated with IVT + EVT versus IVT alone. Results: In all, 1037 patients were included. After propensity score matching (n = 312 per group), IVT + EVT was independently associated with poor functional outcomes (adjusted odds ratio [aOR] 0.46 for mRS 0–1, 95% confidence interval [CI] 0.30–0.72, p = 0.001; aOR 0.52 for mRS 0–2, 95% CI 0.32–0.84, p = 0.007; aOR 1.61 for 1‐point shift in mRS score, 95% CI 1.12–2.32, p = 0.011), with no significant differences in safety outcomes compared to IVT alone, despite numerically higher rates of symptomatic intracerebral haemorrhage (3.3% vs. 1.1%; p = 0.082), a higher rate of any haemorrhagic transformation (17.6% vs. 7.3%; p < 0.001) and subarachnoid haemorrhage (7.9% vs. 1.5%; p = 0.002) in the IVT + EVT group. Discussion: In anterior circulation LVO patients presenting with NIHSS score ≤5, IVT + EVT (vs. IVT alone) was associated with poorer 3‐month functional outcome. Randomized controlled trials are needed to elucidate the best treatments in mild LVO patients. [ABSTRACT FROM AUTHOR]
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- 2023
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56. Autonomic, functional, skeletal muscle, and cardiac abnormalities are associated with increased ergoreflex sensitivity in mitochondrial disease.
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Giannoni, Alberto, Aimo, Alberto, Mancuso, Michelangelo, Piepoli, Massimo Francesco, Orsucci, Daniele, Aquaro, Giovanni Donato, Barison, Andrea, De Marchi, Daniele, Taddei, Claudia, Cameli, Matteo, Raglianti, Valentina, Siciliano, Gabriele, Passino, Claudio, and Emdin, Michele
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HEART disease diagnosis , *EXERCISE physiology , *ECHOCARDIOGRAPHY , *CARDIAC magnetic resonance imaging , *MITOCHONDRIAL pathology - Abstract
Aims: Mitochondrial disease (MD) is a genetic disorder affecting skeletal muscles, with possible myocardial disease. The ergoreflex, sensitive to skeletal muscle work, regulates ventilatory and autonomic responses to exercise. We hypothesized the presence of an increased ergoreflex sensitivity in MD patients, its association with abnormal ventilatory and autonomic responses, and possibly with subclinical cardiac involvement.Methods and Results: Twenty-five MD patients (aged 46 ± 3 years, 32% male) with skeletal myopathy but without known cardiac disease, underwent a thorough evaluation including BNPs, galectin-3, soluble suppression of tumorigenesis 2 (sST2), high sensitivity troponin T/I, catecholamines, ECG, 24-h ECG recording, cardiopulmonary exercise testing, echocardiography, cardiac/muscle magnetic resonance (C/MMR), and ergoreflex assessment. Thirteen age- and sex-matched healthy controls were chosen. Among these myopathic patients, subclinical cardiac damage was detected in up to 80%, with 44% showing fibrosis at CMR. Ergoreflex sensitivity was markedly higher in patients than in controls (64% vs. 37%, P < 0.001), and correlated with muscle fat to water ratio and extracellular volume at MMR (both P < 0.05). Among patients, ergoreflex sensitivity was higher in those with cardiac involvement (P = 0.034). Patients showed a lower peak oxygen consumption (VO2 /kg) than controls (P < 0.001), as well as ventilatory inefficiency (P = 0.024). Ergoreflex sensitivity correlated with reduced workload and peak VO2 /kg (both P < 0.001), and several indicators of autonomic imbalance (P < 0.05). Plasma norepinephrine was the unique predictor of myocardial fibrosis at univariate analysis (P < 0.05).Conclusions: Skeletal myopathy in MD is characterized by enhanced ergoreflex sensitivity, which is associated with a higher incidence of cardiac involvement, exercise intolerance, and sympathetic activation. [ABSTRACT FROM AUTHOR]- Published
- 2017
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57. Autonomic, functional, skeletal muscle, and cardiac abnormalities are associated with increased ergoreflex sensitivity in mitochondrial disease.
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Giannoni, Alberto, Aimo, Alberto, Mancuso, Michelangelo, Piepoli, Massimo Francesco, Orsucci, Daniele, Aquaro, Giovanni Donato, Barison, Andrea, De Marchi, Daniele, Taddei, Claudia, Cameli, Matteo, Raglianti, Valentina, Siciliano, Gabriele, Passino, Claudio, and Emdin, Michele
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ABNORMAL reflexes , *CARCINOGENESIS , *BIOMARKERS , *CARDIOPULMONARY system , *CATECHOLAMINES , *ECHOCARDIOGRAPHY , *ELECTROCARDIOGRAPHY , *EXERCISE tests , *MAGNETIC resonance imaging , *MITOCHONDRIAL pathology , *MOVEMENT disorders , *MUSCLE diseases , *CARDIOMYOPATHIES , *NORADRENALINE , *PROTEINS , *RESPIRATORY insufficiency , *RESPIRATORY muscles , *STATISTICS , *FIBROSIS , *SKELETAL muscle , *AUTONOMIC dysreflexia , *TROPONIN , *DISEASE complications - Abstract
Aims Mitochondrial disease (MD) is a genetic disorder affecting skeletal muscles, with possible myocardial disease. The ergoreflex, sensitive to skeletal muscle work, regulates ventilatory and autonomic responses to exercise. We hypothesized the presence of an increased ergoreflex sensitivity in MD patients, its association with abnormal ventilatory and autonomic responses, and possibly with subclinical cardiac involvement. Methods and results Twenty-five MD patients (aged 46 ± 3 years, 32% male) with skeletal myopathy but without known cardiac disease, underwent a thorough evaluation including BNPs, galectin-3, soluble suppression of tumorigenesis 2 (sST2), high sensitivity troponin T/I, catecholamines, ECG, 24-h ECG recording, cardiopulmonary exercise testing, echocardiography, cardiac/muscle magnetic resonance (C/MMR), and ergoreflex assessment. Thirteen age- and sex-matched healthy controls were chosen. Among these myopathic patients, subclinical cardiac damage was detected in up to 80%, with 44% showing fibrosis at CMR. Ergoreflex sensitivity was markedly higher in patients than in controls (64% vs. 37%, P < 0.001), and correlated with muscle fat to water ratio and extracellular volume at MMR (both P < 0.05). Among patients, ergoreflex sensitivity was higher in those with cardiac involvement (P = 0.034). Patients showed a lower peak oxygen consumption (VO2/kg) than controls (P < 0.001), as well as ventilatory inefficiency (P = 0.024). Ergoreflex sensitivity correlated with reduced workload and peak VO2/kg (both P < 0.001), and several indicators of autonomic imbalance (P < 0.05). Plasma norepinephrine was the unique predictor of myocardial fibrosis at univariate analysis (P < 0.05). Conclusions Skeletal myopathy in MD is characterized by enhanced ergoreflex sensitivity, which is associated with a higher incidence of cardiac involvement, exercise intolerance, and sympathetic activation. [ABSTRACT FROM AUTHOR]
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- 2017
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58. Pathophysiology and Management of Fatigue in Neuromuscular Diseases.
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Torri, Francesca, Lopriore, Piervito, Montano, Vincenzo, Siciliano, Gabriele, Mancuso, Michelangelo, and Ricci, Giulia
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NEUROMUSCULAR diseases , *FATIGUE (Physiology) , *SPINAL muscular atrophy , *MUSCULAR dystrophy , *PATHOLOGICAL physiology , *NEUROMUSCULAR transmission - Abstract
Fatigue is a major determinant of quality of life and motor function in patients affected by several neuromuscular diseases, each of them characterized by a peculiar physiopathology and the involvement of numerous interplaying factors. This narrative review aims to provide an overview on the pathophysiology of fatigue at a biochemical and molecular level with regard to muscular dystrophies, metabolic myopathies, and primary mitochondrial disorders with a focus on mitochondrial myopathies and spinal muscular atrophy, which, although fulfilling the definition of rare diseases, as a group represent a representative ensemble of neuromuscular disorders that the neurologist may encounter in clinical practice. The current use of clinical and instrumental tools for fatigue assessment, and their significance, is discussed. A summary of therapeutic approaches to address fatigue, encompassing pharmacological treatment and physical exercise, is also overviewed. [ABSTRACT FROM AUTHOR]
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- 2023
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59. Iron-sensitive MR imaging of the primary motor cortex to differentiate hereditary spastic paraplegia from other motor neuron diseases.
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Cosottini, Mirco, Donatelli, Graziella, Ricca, Ivana, Bianchi, Francesca, Frosini, Daniela, Montano, Vincenzo, Migaleddu, Gianmichele, Del Prete, Eleonora, Tessa, Alessandra, Cecchi, Paolo, D'Amelio, Claudio, Siciliano, Gabriele, Mancuso, Michelangelo, and Santorelli, Filippo Maria
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Objectives: Hereditary spastic paraplegia (HSP) is a group of genetic neurodegenerative diseases characterised by upper motor neuron (UMN) impairment of the lower limbs. The differential diagnosis with primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) can be challenging. As microglial iron accumulation was reported in the primary motor cortex (PMC) of ALS cases, here we assessed the radiological appearance of the PMC in a cohort of HSP patients using iron-sensitive MR imaging and compared the PMC findings among HSP, PLS, and ALS patients. Methods: We included 3-T MRI scans of 23 HSP patients, 7 PLS patients with lower limb onset, 8 ALS patients with lower limb and prevalent UMN onset (UMN-ALS), and 84 ALS patients with any other clinical picture. The PMC was visually rated on 3D T2*-weighted images as having normal signal intensity, mild hypointensity, or marked hypointensity, and differences in the frequency distribution of signal intensity among the diseases were investigated. Results: The marked hypointensity in the PMC was visible in 3/22 HSP patients (14%), 7/7 PLS patients (100%), 6/8 UMN-ALS patients (75%), and 35/84 ALS patients (42%). The frequency distribution of normal signal intensity, mild hypointensity, and marked hypointensity in HSP patients was different than that in PLS, UMN-ALS, and ALS patients (p < 0.01 in all cases). Conclusions: Iron-sensitive imaging of the PMC could provide useful information in the diagnostic work - up of adult patients with a lower limb onset UMN syndrome, as the cortical hypointensity often seen in PLS and ALS cases is apparently rare in HSP patients. Key Points: • The T2* signal intensity of the primary motor cortex was investigated in patients with HSP, PLS with lower limb onset, and ALS with lower limb and prevalent UMN onset (UMN-ALS) using a clinical 3-T MRI sequence. • Most HSP patients had normal signal intensity in the primary motor cortex (86%); on the contrary, all the PLS and the majority of UMN-ALS patients (75%) had marked cortical hypointensity. • The T2*-weighted imaging of the primary motor cortex could provide useful information in the differential diagnosis of sporadic adult-onset UMN syndromes. [ABSTRACT FROM AUTHOR]
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- 2022
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60. Mitochondrial Epilepsy, a Challenge for Neurologists.
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Lopriore, Piervito, Gomes, Fábio, Montano, Vincenzo, Siciliano, Gabriele, and Mancuso, Michelangelo
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MITOCHONDRIA , *EPILEPSY , *INBORN errors of metabolism , *DNA polymerases , *NEUROLOGISTS , *ENERGY metabolism , *MITOCHONDRIAL DNA - Abstract
Primary mitochondrial diseases are relatively common inborn errors of energy metabolism, with a combined prevalence of 1 in 4300. These disorders typically affect tissues with high energy requirements, including the brain. Epilepsy affects >1% of the worldwide population, making it one of the most common neurological illnesses; it may be the presenting feature of a mitochondrial disease, but is often part of a multisystem clinical presentation. The major genetic causes of mitochondrial epilepsy are mutations in mitochondrial DNA and in the nuclear-encoded gene POLG. Treatment of mitochondrial epilepsy may be challenging, often representing a poor prognostic feature. This narrative review will cover the most recent advances in the field of mitochondrial epilepsy, from pathophysiology and genetic etiologies to phenotype and treatment options. [ABSTRACT FROM AUTHOR]
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- 2022
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61. The Role of Amyloid-β, Tau, and α-Synuclein Proteins as Putative Blood Biomarkers in Patients with Cerebral Amyloid Angiopathy.
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Piccarducci, Rebecca, Caselli, Maria Chiara, Zappelli, Elisa, Ulivi, Leonardo, Daniele, Simona, Siciliano, Gabriele, Ceravolo, Roberto, Mancuso, Michelangelo, Baldacci, Filippo, and Martini, Claudia
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ALZHEIMER'S disease diagnosis , *ALZHEIMER'S disease , *NERVE tissue proteins , *SYNUCLEINS , *CEREBRAL amyloid angiopathy , *NEURODEGENERATION , *PEPTIDES - Abstract
Background: Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder characterized by the deposition of amyloid-β protein (Aβ) within brain blood vessels that develops in elderly people and Alzheimer's disease (AD) patients. Therefore, the investigation of biomarkers able to differentiate CAA patients from AD patients and healthy controls (HC) is of great interest, in particular in peripheral fluids.Objective: The current study aimed to detect the neurodegenerative disease (ND)-related protein (i.e., Aβ1-40, Aβ1-42, tau, and α-synuclein) levels in both red blood cells (RBCs) and plasma of CAA patients and HC, evaluating their role as putative peripheral biomarkers for CAA.Methods: For this purpose, the proteins' concentration was quantified in RBCs and plasma by homemade immunoenzymatic assays in an exploratory cohort of 20 CAA patients and 20 HC.Results: The results highlighted a significant increase of Aβ1-40 and α-synuclein concentrations in both RBCs and plasma of CAA patients, while higher Aβ1-42 and t-tau levels were detected only in RBCs of CAA individuals compared to HC. Moreover, Aβ1-42/Aβ1-40 ratio increased in RBCs and decreased in plasma of CAA patients. The role of these proteins as candidate peripheral biomarkers easily measurable with a blood sample in CAA needs to be confirmed in larger studies.Conclusion: In conclusion, we provide evidence concerning the possible use of blood biomarkers for contributing to CAA diagnosis and differentiation from other NDs. [ABSTRACT FROM AUTHOR]- Published
- 2022
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62. Are white matter abnormalities associated with “unexplained dizziness”?
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Ahmad, Hena, Cerchiai, Niccolò, Mancuso, Michelangelo, Casani, Augusto P., and Bronstein, Adolfo M.
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WHITE matter (Nerve tissue) , *DIZZINESS , *TERTIARY care , *CEREBELLAR ataxia , *RETROSPECTIVE studies - Abstract
Introduction Although cerebral small vessel disease is a significant contributor to the development of imbalance and falls in the elderly, whether it causes dizziness is not known. Methods A retrospective case analysis was conducted for 122 dizzy patients referred to two neuro-otology tertiary centres in London and Pisa. Patients were divided into ‘explained’ causes of dizziness (e.g. benign positional vertigo, vestibular neuritis, orthostatic hypotension, cerebellar ataxias) and ‘unexplained’ dizziness. White matter hyperintensities (WMH) in MRI (T2 weighted and FLAIR sequences) were blindly rated according to the Fazekas scale. Results 122 patients; 58 (mean age = 72, SD = 7.95 years) in the ‘ unexplained ’ group and 64 (mean age = 72.01, SD = 8.28 years) in the ‘ explained ’ group were recruited. The overall frequency of lesions (Fazekas 1–3) significantly differed between groups (p = 0.011). The frequency of severe lesions (Fazekas 3) was significantly higher in the ‘ unexplained ’ group (22%) than in the ‘ explained ’ group (5%; p = 0.003). Conclusion Increased severity of WMH in cases of unexplained dizziness suggests that such abnormalities are likely contributory to the development of dizziness. WM lesions may induce dizziness either because patients perceive a degree of objective unsteadiness or by a disconnection syndrome involving vestibular or locomotor areas of the brain. [ABSTRACT FROM AUTHOR]
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- 2015
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63. The use of digital tools in rare neurological diseases towards a new care model: a narrative review.
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Torri, Francesca, Vadi, Gabriele, Meli, Adriana, Loprieno, Sara, Schirinzi, Erika, Lopriore, Piervito, Ricci, Giulia, Siciliano, Gabriele, and Mancuso, Michelangelo
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Rare neurological diseases as a whole share peculiar features as motor and/or cognitive impairment, an elevated disability burden, a frequently chronic course and, in present times, scarcity of therapeutic options. The rarity of those conditions hampers both the identification of significant prognostic outcome measures, and the development of novel therapeutic approaches and clinical trials. Collection of objective clinical data through digital devices can support diagnosis, care, and therapeutic research. We provide an overview on recent developments in the field of digital tools applied to rare neurological diseases, both in the care setting and as providers of outcome measures in clinical trials in a representative subgroup of conditions, including ataxias, hereditary spastic paraplegias, motoneuron diseases and myopathies. [ABSTRACT FROM AUTHOR]
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- 2024
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64. Mitochondrial Ataxias: Molecular Classification and Clinical Heterogeneity.
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Lopriore, Piervito, Ricciarini, Valentina, Siciliano, Gabriele, Mancuso, Michelangelo, and Montano, Vincenzo
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CEREBELLAR nuclei , *MITOCHONDRIA , *HETEROGENEITY , *ATAXIA , *CLASSIFICATION - Abstract
Ataxia is increasingly being recognized as a cardinal manifestation in primary mitochondrial diseases (PMDs) in both paediatric and adult patients. It can be caused by disruption of cerebellar nuclei or fibres, its connection with the brainstem, or spinal and peripheral lesions leading to proprioceptive loss. Despite mitochondrial ataxias having no specific defining features, they should be included in hereditary ataxias differential diagnosis, given the high prevalence of PMDs. This review focuses on the clinical and neuropathological features and genetic background of PMDs in which ataxia is a prominent manifestation. [ABSTRACT FROM AUTHOR]
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- 2022
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65. Adult-onset mitochondrial movement disorders: a national picture from the Italian Network.
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Montano, V., Orsucci, D., Carelli, V., La Morgia, C., Valentino, M. L., Lamperti, C., Marchet, S., Musumeci, O., Toscano, A., Primiano, G., Santorelli, F. M., Ticci, C., Filosto, M., Rubegni, A., Mongini, T., Tonin, P., Servidei, S., Ceravolo, R., Siciliano, G., and Mancuso, Michelangelo
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MOVEMENT disorders , *MITOCHONDRIAL pathology , *BASAL ganglia , *DIAGNOSIS , *GENETIC testing , *WHITE matter (Nerve tissue) , *PARKINSONIAN disorders - Abstract
Introduction: Both prevalence and clinical features of the various movement disorders in adults with primary mitochondrial diseases are unknown. Methods: Based on the database of the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases", we reviewed the clinical, genetic, neuroimaging and neurophysiological data of adult patients with primary mitochondrial diseases (n = 764) where ataxia, myoclonus or other movement disorders were part of the clinical phenotype. Results: Ataxia, myoclonus and movement disorders were present in 105/764 adults (13.7%), with the onset coinciding or preceding the diagnosis of the mitochondrial disease in 49/105 (46.7%). Ataxia and parkinsonism were the most represented, with an overall prevalence at last follow-up of 59.1% and 30.5%, respectively. Hyperkinetic movement disorders were reported in 15.3% at last follow-up, being the less common reported movement disorders. The pathogenic m.8344A > G and POLG variants were always associated with a movement disorder, while LHON variants and mtDNA single deletions were more commonly found in the subjects who did not present a movement disorder. The most common neuroimaging features were cortical and/or cerebellar atrophy, white matter hyperintensities, basal ganglia abnormalities and nigro-striatal degeneration. Almost 70% of patients with parkinsonism responded to dopaminergic therapy, mainly levodopa, and 50% with myoclonus were successfully treated with levetiracetam. Conclusion: Movement disorders, mainly ataxia and parkinsonism, are important findings in adult primary mitochondrial diseases. This study underlies the importance of looking for a mitochondrial etiology in the diagnostic flowchart of a movement disorder and may help direct genetic screening in daily practice. [ABSTRACT FROM AUTHOR]
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- 2022
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66. Twinkle mutation in an Italian family with external progressive ophthalmoplegia and parkinsonism: A case report and an update on the state of art.
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Kiferle, Lorenzo, Orsucci, Daniele, Mancuso, Michelangelo, Lo Gerfo, Annalisa, Petrozzi, Lucia, Siciliano, Gabriele, Ceravolo, Roberto, and Bonuccelli, Ubaldo
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GENETIC mutation , *EYE paralysis , *PHENOTYPES , *BRAIN imaging , *SINGLE photon emission computerized tomography centers , *HELICASES - Abstract
Highlights: [•] We here describe a family with two sisters and one son affected by a PEO1 mutation. [•] The sisters had a clinical parkinsonism confirmed by FP-CIT SCAN. [•] The characteristics of parkinsonisms are fully described in the paper. [•] The paper provides a short review of the phenotypes of the parkinsonisms associated to PEO1 mutation described in the literature. [Copyright &y& Elsevier]
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- 2013
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67. Genome‐Wide Association Study Identifies First Locus Associated with Susceptibility to Cerebral Venous Thrombosis.
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Ken‐Dror, Gie, Cotlarciuc, Ioana, Martinelli, Ida, Grandone, Elvira, Hiltunen, Sini, Lindgren, Erik, Margaglione, Maurizio, Duchez, Veronique Le Cam, Triquenot, Aude Bagan, Zedde, Marialuisa, Mancuso, Michelangelo, Ruigrok, Ynte M., Marjot, Thomas, Worrall, Brad, Majersik, Jennifer J., Metso, Tiina M., Putaala, Jukka, Haapaniemi, Elena, Zuurbier, Susanna M., and Brouwer, Matthijs C.
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GENOME-wide association studies , *GENETIC variation , *ABO blood group system , *CEREBRAL embolism & thrombosis , *VENOUS thrombosis , *LOCUS (Genetics) - Abstract
Objective: Cerebral venous thrombosis (CVT) is an uncommon form of stroke affecting mostly young individuals. Although genetic factors are thought to play a role in this cerebrovascular condition, its genetic etiology is not well understood. Methods: A genome‐wide association study was performed to identify genetic variants influencing susceptibility to CVT. A 2‐stage genome‐wide study was undertaken in 882 Europeans diagnosed with CVT and 1,205 ethnicity‐matched control subjects divided into discovery and independent replication datasets. Results: In the overall case–control cohort, we identified highly significant associations with 37 single nucleotide polymorphisms (SNPs) within the 9q34.2 region. The strongest association was with rs8176645 (combined p = 9.15 × 10−24; odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.76–2.31). The discovery set findings were validated across an independent European cohort. Genetic risk score for this 9q34.2 region increases CVT risk by a pooled estimate OR = 2.65 (95% CI = 2.21–3.20, p = 2.00 × 10−16). SNPs within this region were in strong linkage disequilibrium (LD) with coding regions of the ABO gene. The ABO blood group was determined using allele combination of SNPs rs8176746 and rs8176645. Blood groups A, B, or AB, were at 2.85 times (95% CI = 2.32–3.52, p = 2.00 × 10−16) increased risk of CVT compared with individuals with blood group O. Interpretation: We present the first chromosomal region to robustly associate with a genetic susceptibility to CVT. This region more than doubles the likelihood of CVT, a risk greater than any previously identified thrombophilia genetic risk marker. That the identified variant is in strong LD with the coding region of the ABO gene with differences in blood group prevalence provides important new insights into the pathophysiology of CVT. ANN NEUROL 2021;90:777–788 [ABSTRACT FROM AUTHOR]
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- 2021
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68. A novel mitochondrial tRNAIle point mutation associated with chronic progressive external ophthalmoplegia and hyperCKemia
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Souilem, Sihem, Chebel, Saber, Mancuso, Michelangelo, Petrozzi, Lucia, Siciliano, Gabriele, FrihAyed, Mahbouba, Hentati, Faycal, and Amouri, Rim
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TRANSFER RNA , *MITOCHONDRIA , *GENETIC mutation , *EYE paralysis , *DISEASE progression , *NUCLEOTIDE sequence , *BIOCHEMISTRY , *HETEROGENEITY - Abstract
Abstract: We have sequenced the entire mitochondrial DNA (mtDNA) from a 54-year-old man with chronic progressive external ophthalmoplegia (PEO) and hyperCKemia. Muscle biopsy showed ragged red and SDH positive/COX negative fibres, and the biochemistry was suggestive mitochondrial respiratory chain dysfunction. Analysis of mtDNA revealed a heteroplasmic m. 4308G>A mutation in the transfer RNA isoleucine gene (MT-TI gene). Our report expands the genetic heterogeneity of PEO. [Copyright &y& Elsevier]
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- 2011
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69. D90A-SOD1 mutation in ALS: The first report of heterozygous Italian patients and unusual findings.
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Giannini, Fabio, Battistini, Stefania, Mancuso, Michelangelo, Greco, Giuseppe, Ricci, Claudia, Volpi, Nila, Del Corona, Alberto, Piazza, Selina, and Siciliano, Gabriele
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AMYOTROPHIC lateral sclerosis , *SUPEROXIDE dismutase , *GENETIC mutation , *SENSORY neurons , *BIOPSY - Abstract
Among the 140 Cu/Zn superoxide dismutase-1 (SOD1) gene mutations associated with ALS, only D90A, the most prevalent mutation in Europe, has been clearly shown to cause recessive and dominant ALS. Here we first describe two, apparently sporadic, Italian ALS patients heterozygous for the D90A mutation. One patient experienced early sensory involvement, confirmed by nerve biopsy. We review sensory symptoms in SOD1 ALS and discuss its possible origin in D90A heterozygous patients. [ABSTRACT FROM AUTHOR]
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- 2010
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70. Clinical, imaging, biochemical and molecular features in Leigh syndrome: a study from the Italian network of mitochondrial diseases.
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Ardissone, Anna, Bruno, Claudio, Diodato, Daria, Donati, Alice, Ghezzi, Daniele, Lamantea, Eleonora, Lamperti, Costanza, Mancuso, Michelangelo, Martinelli, Diego, Primiano, Guido, Procopio, Elena, Rubegni, Anna, Santorelli, Filippo, Schiaffino, Maria Cristina, Servidei, Serenella, Tubili, Flavia, Bertini, Enrico, and Moroni, Isabella
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MITOCHONDRIA , *PROGNOSIS , *CENTRAL nervous system , *MITOCHONDRIAL pathology , *OXIDATIVE phosphorylation , *PROTEINS , *RESEARCH , *GENETIC mutation , *RESEARCH methodology , *MEDICAL cooperation , *EVALUATION research , *COMPARATIVE studies , *RESEARCH funding , *LEIGH disease , *MEMBRANE proteins - Abstract
Background: Leigh syndrome (LS) is a progressive neurodegenerative disorder associated with primary or secondary dysfunction of mitochondrial oxidative phosphorylation and is the most common mitochondrial disease in childhood. Numerous reports on the biochemical and molecular profiles of LS have been published, but there are limited studies on genetically confirmed large series. We reviewed the clinical, imaging, biochemical and molecular data of 122 patients with a diagnosis of LS collected in the Italian Collaborative Network of Mitochondrial Diseases database.Results: Clinical picture was characterized by early onset of several neurological signs dominated by central nervous system involvement associated with both supra- and sub-tentorial grey matter at MRI in the majority of cases. Extraneurological organ involvement is less frequent in LS than expected for a mitochondrial disorder. Complex I and IV deficiencies were the most common biochemical diagnoses, mostly associated with mutations in SURF1 or mitochondrial-DNA genes encoding complex I subunits. Our data showed SURF1 as the genotype with the most unfavorable prognosis, differently from other cohorts reported to date.Conclusion: We report on a large genetically defined LS cohort, adding new data on phenotype-genotype correlation, prognostic factors and possible suggestions to diagnostic workup. [ABSTRACT FROM AUTHOR]- Published
- 2021
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71. Mitochondrial disease in adults: recent advances and future promise.
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Ng, Yi Shiau, Bindoff, Laurence A, Gorman, Gráinne S, Klopstock, Thomas, Kornblum, Cornelia, Mancuso, Michelangelo, McFarland, Robert, Sue, Carolyn M, Suomalainen, Anu, Taylor, Robert W, Thorburn, David R, and Turnbull, Doug M
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MITOCHONDRIAL pathology , *ADULTS , *MITOCHONDRIA , *NUCLEOTIDE sequencing , *REPRODUCTIVE technology , *SMALL molecules - Abstract
Mitochondrial diseases are some of the most common inherited neurometabolic disorders, and major progress has been made in our understanding, diagnosis, and treatment of these conditions in the past 5 years. Development of national mitochondrial disease cohorts and international collaborations has changed our knowledge of the spectrum of clinical phenotypes and natural history of mitochondrial diseases. Advances in high-throughput sequencing technologies have altered the diagnostic algorithm for mitochondrial diseases by increasingly using a genetics-first approach, with more than 350 disease-causing genes identified to date. While the current management strategy for mitochondrial disease focuses on surveillance for multisystem involvement and effective symptomatic treatment, new endeavours are underway to find better treatments, including repurposing current drugs, use of novel small molecules, and gene therapies. Developments made in reproductive technology offer women the opportunity to prevent transmission of DNA-related mitochondrial disease to their children. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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72. Magnitude of blood pressure change and clinical outcomes after thrombectomy in stroke caused by large artery occlusion.
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Anadani, Mohammad, Matusevicius, Marius, Tsivgoulis, Georgios, Peeters, André, Nunes, Ana Paiva, Mancuso, Michelangelo, Roffe, Christine, Havenon, Adam, and Ahmed, Niaz
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ARTERIAL occlusions , *BLOOD pressure , *TREATMENT effectiveness , *THROMBECTOMY , *SYSTOLIC blood pressure - Abstract
Background: Extremes of both high and low systolic blood pressure (SBP) after mechanical thrombectomy (MT) in large artery occlusion stroke are known predictors of unfavorable outcome. However, the effect of SBP change (∆SBP) during the first 24 h on thrombectomy outcomes remains unclear. We aimed to investigate the association between ∆SBP at different time intervals and thrombectomy outcomes. Methods: We analyzed MT‐treated patients registered in the SITS International Stroke Thrombectomy Registry from January 1, 2014 to September 3, 2019. Primary outcome was 3‐month unfavorable outcome (modified Rankin scale scores 3–6). We defined ∆SBP as the mean SBP of a given time interval after MT (0–2, 2–4, 4–12, 12–24 h) minus admission SBP. Multivariable mixed logistic regression models were used to adjust for known confounders and center as random effect. Subgroup analyses were included to contrast specific subpopulations. Restricted cubic splines were used to model the associations. Results: The study population consisted of 5835 patients (mean age 70 years, 51% male, median NIHSS 16). Mean ∆SBP was −12.3, −15.7, −17.2, and −16.9 mmHg for the time intervals 0–2, 2–4, 4–12 h, and 12–24 h, respectively. Higher ∆SBP was associated with unfavorable outcome at 0–2 h (odds ratio 1.065, 95% confidence interval 1.014–1.118), 2–4 h (1.140, 1.081–1.203), 4–12 h (1.145, 1.087–1.203), and 12–24 h (1.145, 1.089–1.203), for every increase of 10 mmHg. Restricted cubic spline models suggested that increasing ∆SBP was associated with unfavorable outcome, with higher values showing increased risk of unfavorable outcome. Conclusion: SBP increase after thrombectomy in large artery occlusion stroke is associated with poor functional outcome. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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73. Assessing awareness and care practices for rare neurologic diseases among esteemed World Federation of Neurology (WFN) members: A global survey.
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Gyu Jang, Day, Federico, Antonio, Feldman, Eva L., Grisold, Wolfgang, Hunte, Carlos, Mancuso, Michelangelo, Judit Molnar, Maria, and Reynolds, Evan
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NEUROLOGICAL disorders , *INTERNATIONAL organization , *NEUROLOGY , *AWARENESS - Published
- 2023
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74. Oxidative stress biomarkers in Fabry disease: is there a room for them?
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Simoncini, C., Torri, S., Montano, V., Chico, L., Gruosso, F., Tuttolomondo, A., Pinto, A., Simonetta, I., Cianci, V., Salviati, A., Vicenzi, V., Marchi, G., Girelli, D., Concolino, D., Sestito, S., Zedde, M., Siciliano, G., and Mancuso, Michelangelo
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ANGIOKERATOMA corporis diffusum , *OXIDATIVE stress , *BIOMARKERS , *LYSOSOMAL storage diseases , *DISEASE progression , *GLYCOGEN storage disease type II , *MULTIPLE system atrophy - Abstract
Background: Fabry disease (FD) is an X-linked lysosomal storage disorder, caused by deficient activity of the alpha-galactosidase A enzyme leading to progressive and multisystemic accumulation of globotriaosylceramide. Recent data point toward oxidative stress signalling which could play an important role in both pathophysiology and disease progression. Methods: We have examined oxidative stress biomarkers [Advanced Oxidation Protein Products (AOPP), Ferric Reducing Antioxidant Power (FRAP), thiolic groups] in blood samples from 60 patients and 77 healthy controls. Results: AOPP levels were higher in patients than in controls (p < 0.00001) and patients presented decreased levels of antioxidant defences (FRAP and thiols) with respect to controls (p < 0.00001). In a small group of eight treatment-naïve subjects with FD-related mutations, we found altered levels of oxidative stress parameters and incipient signs of organ damage despite normal lyso-Gb3 levels. Conclusions: Oxidative stress occurs in FD in both treated and naïve patients, highlighting the need of further research in oxidative stress-targeted therapies. Furthermore, we found that oxidative stress biomarkers may represent early markers of disease in treatment-naïve patients with a potential role in helping interpretation of FD-related mutations and time to treatment decision. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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75. Fibroblast growth factor 21 and grow differentiation factor 15 are sensitive biomarkers of mitochondrial diseases due to mitochondrial transfer-RNA mutations and mitochondrial DNA deletions.
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Formichi, Patrizia, Cardone, Nastasia, Taglia, Ilaria, Cardaioli, Elena, Salvatore, Simona, Gerfo, Annalisa Lo, Simoncini, Costanza, Montano, Vincenzo, Siciliano, Gabriele, Mancuso, Michelangelo, Malandrini, Alessandro, Federico, Antonio, and Dotti, Maria Teresa
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FIBROBLAST growth factors , *MITOCHONDRIAL DNA , *BIOMARKERS , *EYE paralysis , *LEBER'S hereditary optic atrophy , *DIAGNOSIS - Abstract
Background: Diagnosis of mitochondrial diseases (MDs) is challenging, since they are multisystemic disorders, characterized by a heterogeneous symptomatology. Recently, an increase in serum levels of fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) has been found in the majority of patients with MDs compared with healthy controls. On the other hand, the finding of low FGF21 and GDF15 levels in some patients with MDs suggests that different types of respiratory chain defects may lead to different profiles of these two proteins. Objective: In this study, we aimed to validate the diagnostic reliability of FGF21 and GDF15 assays in MDs and to evaluate a possible correlation between serum levels of the two biomarkers with genotype of MD patients. Serum FGF21 and GDF15 levels were measured by a quantitative ELISA. Results: Our results showed increased serum FGF21 and GDF15 levels in MD patients; however, GDF15 measurement seems to be more sensitive and specific for screening tests for MD than FGF21. Moreover, we showed a positive correlation with both FGF21 and GDF15 levels and the number of COX-negative fibers. Conclusion: Finally, we also demonstrated that the increase of FGF21 and GDF15 was related to MDs caused by mitochondrial translation defects, and multiple and single mtDNA deletions, but not to MDs due to mutations in the respiratory chain subunits. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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76. An "all-wheel drive" proposal to accelerate clinical research in common and rare neurological diseases.
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Salvetti, Marco, Battaglia, Mario A., Di Filippo, Massimiliano, Mancardi, Gian Luigi, Mancuso, Michelangelo, Patti, Francesco, Sormani, Maria Pia, and Zaratin, Paola
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NEUROLOGICAL disorders , *RARE diseases , *BUSINESS models , *BIOLOGY , *MULTIPLE sclerosis - Abstract
The complex biology of neurological diseases calls for collaborative efforts that may increase the success rate of clinical research. Models have been proposed, but concrete actions remain insufficient. Based on recent considerations from basic science, from science of patient input and from an analysis of scientific resources in Italy, we here explain why our country may represent an appropriate environment for such actions. Furthermore, we sketch operational framework and business model to be applied in order to accelerate, in parallel, the development of therapies in common and rare diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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77. Muscle pain in mitochondrial diseases: a picture from the Italian network.
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Filosto, Massimiliano, Cotti Piccinelli, Stefano, Lamperti, Costanza, Mongini, Tiziana, Servidei, Serenella, Musumeci, Olimpia, Tonin, Paola, Santorelli, Filippo Maria, Simoncini, Costanza, Primiano, Guido, Vercelli, Liliana, Rubegni, Anna, Galvagni, Anna, Moggio, Maurizio, Comi, Giacomo Pietro, Carelli, Valerio, Toscano, Antonio, Padovani, Alessandro, Siciliano, Gabriele, and Mancuso, Michelangelo
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EYE paralysis , *MYALGIA - Abstract
Muscle pain may be part of many neuromuscular disorders including myopathies, peripheral neuropathies and lower motor neuron diseases. Although it has been reported also in mitochondrial diseases (MD), no extensive studies in this group of diseases have been performed so far. We reviewed clinical data from 1398 patients affected with mitochondrial diseases listed in the database of the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases", to assess muscle pain and its features. Muscle pain was present in 164 patients (11.7%). It was commonly observed in subjects with chronic progressive external ophthalmoplegia (cPEO) and with primary myopathy without cPEO, but also—although less frequently—in multisystem phenotypes such as MELAS, MERFF, Kearns Sayre syndrome, NARP, MNGIE and Leigh syndrome. Patients mainly complain of diffuse exercise-related muscle pain, but focal/multifocal and at rest myalgia were often also reported. Muscle pain was more commonly detected in patients with mitochondrial DNA mutations (67.8%) than with nuclear DNA changes (32.2%). Only 34% of the patients showed a good response to drug therapy. Interestingly, patients with nuclear DNA mutations tend to have a better therapeutic response than patients with mtDNA mutations. Muscle pain is present in a significant number of patients with MD, being one of the most common symptoms. Although patients with a myopathic phenotype are more prone to develop muscle pain, this is also observed in patients with a multi system involvement, representing an important and disabling symptom having poor response to current therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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78. Disruption of sleep-wake continuum in myotonic dystrophy type 1: Beyond conventional sleep staging.
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Bonanni, Enrica, Carnicelli, Luca, Crapanzano, Davide, Maestri, Michelangelo, Simoncini, Costanza, Baldanzi, Sigrid, Falorni, Michela, Garbarino, Sergio, Mancuso, Michelangelo, Bonuccelli, Ubaldo, and Siciliano, Gabriele
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MYOTONIA atrophica , *SLEEP apnea syndromes , *COGNITIVE therapy , *RAPID eye movement sleep , *METHYLENE blue , *THERAPEUTICS - Abstract
Sleep disruption and excessive daytime sleepiness are well recognised symptoms in myotonic dystrophy type 1 (DM1), where a central dysfunction of sleep-wake regulation may play a pivotal role. Few studies evaluated sleep macrostructure in DM1, but none investigated more refined sleep variables. Eight DM1 patients (6 male, aged 20-50 years) and 10 healthy controls (7 male, aged 22-67 years) underwent nocturnal polysomnography and multiple sleep latency test. Sleep stages and events were scored according to standard criteria; sleep microstructure was analyzed through cyclic alternating pattern. Relative and absolute delta powers were computed for whole non REM and each non REM period. DM1 patients showed increased REM sleep and decreased N2. N3, although not significantly, was increased. Three patients, but no controls, had sleep-onset REM period in nocturnal sleep. DM1 patients showed slower delta power dissipation across the night, and increased sleep instability (CAP rate). Multiple sleep latency tests showed shorter sleep latencies, five patients presenting at least one sleep-onset REM period and, when including also night sleep, two sleep-onset REM periods. Our data confirm a narcoleptic-like phenotype in DM1 with a prominent REM sleep dysregulation, that may account for daytime sleepiness, together with increased sleep instability and impaired delta power dissipation that seem peculiar of the disease. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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79. Novel POLG mutations and variable clinical phenotypes in 13 Italian patients.
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Da Pozzo, Paola, Cardaioli, Elena, Rubegni, Anna, Gallus, Gian, Malandrini, Alessandro, Rufa, Alessandra, Battisti, Carla, Carluccio, Maria, Rocchi, Raffaele, Giannini, Fabio, Bianchi, Amedeo, Mancuso, Michelangelo, Siciliano, Gabriele, Dotti, Maria, Federico, Antonio, Gallus, Gian Nicola, Carluccio, Maria Alessandra, and Dotti, Maria Teresa
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GENETIC mutation , *PHENOTYPES , *GENES , *DNA polymerases , *MITOCHONDRIAL pathology - Abstract
POLG gene encodes the catalytic subunit of DNA polymerase gamma, essential for mitochondrial DNA (mtDNA) replication and repair. Mutations in POLG have been linked to a spectrum of clinical phenotypes, resulting in autosomal recessive or dominant mitochondrial diseases. These mutations have been associated with heterogeneous phenotypes, presenting with varying severity and at different ages of onset, ranging from the neonatal period to late adult life. We screened 13 patients for POLG mutations. All patients underwent a complete neurological examination, and in most of cases, muscle biopsy was performed. We detected 15 different variations in 13 unrelated Italian patients. Two mutations were novel and mapped in the pol domain (p.Thr989dup and p.Ala847Thr) of the enzyme. We also report new cases carrying controversial variations previously described as incompletely penetrant or a variant of unknown significance. Our study increases the range of clinical presentations associated with mutations in POLG gene, underlining some peculiar clinical features, such as PEO associated with corneal edema, and epilepsy, severe neuropathy with achalasia. The addition of two new substitutions, including the second report of an in-frame duplication, to the growing list of defects increases the value of POLG genetic diagnosis in a range of neurological presentations. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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80. Mitochondrial stroke-like episodes: The search for new therapies.
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Orsucci, Daniele, Caldarazzo Ienco, Elena, Montano, Vincenzo, Siciliano, Gabriele, and Mancuso, Michelangelo
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MITOCHONDRIA , *MITOCHONDRIAL pathology , *LACTIC acidosis , *GENETIC disorders , *ANTICONVULSANTS - Abstract
A mitochondrial stroke-like event is an evolving subacute neurological syndrome linked to seizure activity and focal metabolic brain derangement in a genetically determined mitochondrial disorder. The acronym "MELAS" (mitochondrial encephalopathy associated with lactic acidosis and stroke-like lesions) identifies subjects with molecular, biochemical and/or histological evidence of mitochondrial disorder who experience stroke-like lesions. MELAS is a rare inherited mitochondrial disease linked to severe multiorgan involvement and stress-induced episodes of metabolic decompensation and lactic acidosis. Unfortunately, there are no etiopathogenetic therapies for stroke-like episodes to date, and the treatment is mainly based on anti-epileptic drugs and supportive therapies. This perspective opinion article discusses the current care standards for MELAS patients and revises current and innovative emerging therapies for mitochondrial stroke-like episodes. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2022
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81. Acute encephalopathy of the temporal lobes leading to m.3243A > G. When MELAS is not always MELAS.
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Caldarazzo Ienco, Elena, Orsucci, Daniele, Simoncini, Costanza, Montano, Vincenzo, LoGerfo, Annalisa, Siciliano, Gabriele, Bonuccelli, Ubaldo, and Mancuso, Michelangelo
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MITOCHONDRIAL encephalomyopathies , *GENETIC mutation , *MELAS syndrome , *BRAIN imaging , *GENETIC disorders , *DIAGNOSIS - Abstract
MELAS syndrome (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) is a rare genetic condition whose differential diagnosis is often posed with juvenile stroke, but more rarely even with inflammatory/infectious encephalitis, causing diagnostic challenges. Here we report the case of a young man harbouring the m.3243A > G MELAS mutation presenting an acute onset mimicking the clinical and neuroimaging features of infective encephalitis. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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82. Hereditary spastic paraparesis in adults. A clinical and genetic perspective from Tuscany.
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Orsucci, Daniele, Petrucci, Loredana, Ienco, Elena Caldarazzo, Chico, Lucia, Simi, Paolo, Fogli, Antonella, Baldinotti, Fulvia, Simoncini, Costanza, LoGerfo, Annalisa, Carlesi, Cecilia, Arnoldi, Alessia, Bassi, Maria Teresa, Siciliano, Gabriele, Bonuccelli, Ubaldo, and Mancuso, Michelangelo
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PARAPLEGIA , *MACROMOLECULES , *GENETIC mutation , *GENES , *QUALITY of life , *MAGNETIC resonance imaging - Abstract
Objective: Hereditary spastic paraparesis or paraplegias (HSPs) are a group of neurogenetic conditions with prominent involvement of the pyramidal tracts. Aim of this study is the clinical and molecular characterization of a cohort of patients with HSP. Moreover, we aim to study the minimum prevalence of HSP in our area and to propose a schematic diagnostic approach to HSP patients based on the available data from the literature. Methods: Retrospective/perspective study on the subjects with clinical signs and symptoms indicative of pure or complicated HSP, in whom other possible diagnosis were excluded by appropriate neuroradiological, neurophysiologic and laboratory studies, who have been evaluated by the Neurogenetic Service of our clinic in last two years (2011-2012). Results: 45 patients were identified. The minimum prevalence of HSP in our area was of about 2.17-3.43/100,000. The SF-36 (quality of life) and SPRS (disease progression) scores were inversely related; the timesaving, four-stage scale of motor disability could predict the SPRS scores with a high statistical significance, and we encourage its use in HSP. Our study confirms SPG4 as the major cause of HSP. All SPG4 patients had a pure HSP phenotype, and the dominant inheritance was evident in the great majority of these subjects. SPG7 was the second genetic cause. Other genotypes were rarer (SPG10, SPG11, SPG17). Conclusion: Exact molecular diagnosis will allow a more accurate patient counseling and, hopefully, will lead to specific, targeted, therapeutic options for these chronic, still incurable diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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83. Implication of a Genetic Variant at PICALM in Alzheimer's Disease Patients and Centenarians.
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Piaceri, Irene, Bagnoli, Silvia, Lucenteforte, Ersilia, Mancuso, Michelangelo, Tedde, Andrea, Siciliano, Gabriele, Piacentini, Silvia, Bracco, Laura, Sorbi, Sandro, and Nacmias, Benedetta
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GENETIC polymorphisms , *APOLIPOPROTEINS , *PHOSPHOINOSITIDES , *ALZHEIMER'S disease , *OLDER people , *CENTENARIANS , *LONGEVITY - Abstract
A common polymorphism (rs3851179) in the PICALM (phosphatidylinositol-binding clathrin assembly protein) gene has been recently associated with reduced risk of developing late-onset Alzheimer's disease (LOAD). We analyzed the genotype and allele distributions of the PICALM polymorphism in 813 Italian subjects, including LOAD patients and centenarians. The segregation of the PICALM rs3851179 showed no statistically significant difference between LOAD cases and controls. The implication of a genetic variant at PICALM is confirmed for the first time, in centenarians, thus suggesting a possible role in longevity. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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84. Oxidative Stress Treatment for Clinical Trials in Neurodegenerative Diseases.
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Britton, Gabriel B., Smith, Mark A., Perry, George, Sambamurti, Kumar, Jagannatha Rao, K.S., Ienco, Elena Caldarazzo, LoGerfo, Annalisa, Carlesi, Cecilia, Orsucci, Daniele, Ricci, Giulia, Mancuso, Michelangelo, and Siciliano, Gabriele
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OXIDATIVE stress , *METABOLIC syndrome , *ANTIOXIDANTS , *CLINICAL trials , *TREATMENT of neurodegeneration - Abstract
Oxidative stress is a metabolic condition arising from imbalance between the production of potentially reactive oxygen species and the scavenging activities. Mitochondria are the main providers but also the main scavengers of cell oxidative stress. The role of mitochondrial dysfunction and oxidative stress in the pathogenesis of neurodegenerative diseases is well documented. Therefore, therapeutic approaches targeting mitochondrial dysfunction and oxidative damage hold great promise in neurodegenerative diseases. Despite this evidence, human experience with antioxidant neuroprotectants has generally been negative with regards to the clinical progress of disease, with unclear results in biochemical assays. Here we review the antioxidant approaches performed so far in neurodegenerative diseases and the future challenges in modern medicine. [ABSTRACT FROM AUTHOR]
- Published
- 2011
85. Oxidative Stress Treatment for Clinical Trials in Neurodegenerative Diseases.
- Author
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Ienco, Elena Caldarazzo, LoGerfo, Annalisa, Carlesi, Cecilia, Orsucci, Daniele, Ricci, Giulia, Mancuso, Michelangelo, and Siciliano, Gabriele
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OXIDATIVE stress , *NEURODEGENERATION , *ANTIOXIDANTS , *MITOCHONDRIAL pathology , *OXIDATION-reduction reaction - Abstract
Oxidative stress is a metabolic condition arising from imbalance between the production of potentially reactive oxygen species and the scavenging activities. Mitochondria are the main providers but also the main scavengers of cell oxidative stress. The role of mitochondrial dysfunction and oxidative stress in the pathogenesis of neurodegenerative diseases is well documented. Therefore, therapeutic approaches targeting mitochondrial dysfunction and oxidative damage hold great promise in neurodegenerative diseases. Despite this evidence, human experience with antioxidant neuroprotectants has generally been negative with regards to the clinical progress of disease, with unclear results in biochemical assays. Here we review the antioxidant approaches performed so far in neurodegenerative diseases and the future challenges in modern medicine. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
86. Oxidative stress treatment for clinical trials in neurodegenerative diseases.
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Ienco, Elena Caldarazzo, Logerfo, Annalisa, Carlesi, Cecilia, Orsucci, Daniele, Ricci, Giulia, Mancuso, Michelangelo, and Siciliano, Gabriele
- Abstract
Oxidative stress is a metabolic condition arising from imbalance between the production of potentially reactive oxygen species and the scavenging activities. Mitochondria are the main providers but also the main scavengers of cell oxidative stress. The role of mitochondrial dysfunction and oxidative stress in the pathogenesis of neurodegenerative diseases is well documented. Therefore, therapeutic approaches targeting mitochondrial dysfunction and oxidative damage hold great promise in neurodegenerative diseases. Despite this evidence, human experience with antioxidant neuroprotectants has generally been negative with regards to the clinical progress of disease, with unclear results in biochemical assays. Here we review the antioxidant approaches performed so far in neurodegenerative diseases and the future challenges in modern medicine. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
87. May 'Mitochondrial Eve' and Mitochondrial Haplogroups Play a Role in Neurodegeneration and Alzheimer's Disease?
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Ienco, Elena Caldarazzo, Simoncini, Costanza, Orsucci, Daniele, Petrucci, Loredana, Filosto, Massimiliano, Mancuso, Michelangelo, and Siciliano, Gabriele
- Published
- 2011
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88. May "Mitochondrial Eve" and Mitochondrial Haplogroups Play a Role in Neurodegeneration and Alzheimer's Disease?
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Ienco, Elena Caldarazzo, Simoncini, Costanza, Orsucci, Daniele, Petrucci, Loredana, Filosto, Massimiliano, Mancuso, Michelangelo, and Siciliano, Gabriele
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GENETICS of Alzheimer's disease , *MITOCHONDRIAL physiology , *NEURODEGENERATION , *AGING , *EMIGRATION & immigration , *GENETICS - Abstract
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 species, 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. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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89. G41S SOD1 mutation: A common ancestor for six ALS Italian families with an aggressive phenotype.
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Battistini, Stefania, Ricci, Claudia, Giannini, Fabio, Calzavara, Silvia, Greco, Giuseppe, Del Corona, Alberto, Mancuso, Michelangelo, Battistini, Noè, Siciliano, Gabriele, and Carrera, Paola
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GENETIC mutation , *SUPEROXIDE dismutase , *AMYOTROPHIC lateral sclerosis , *GENETIC research , *FAMILIAL diseases , *PATIENTS - Abstract
More than 140 different mutations have been reported in the Cu/Zn superoxide dismutase-1 ( SOD1) gene in patients with amyotrophic lateral sclerosis (ALS), some occurring as founder mutations. Occasionally, specific mutations are associated with a particular phenotype. We evaluated a possible genotype-phenotype correlation and looked for a founder effect in nine patients from six unrelated families with ALS, all carrying the G41S mutation, originating from north-west Tuscany in central Italy. Mutational analysis of the SOD1 gene was carried out by direct sequencing. A haplotype study was carried out using eight polymorphic markers flanking the SOD1 gene. The clinical pattern of the nine familial ALS (FALS) patients was characterized by spinal onset with early upper and lower motor neuron involvement, appearance of bulbar signs within one year, and death a few months later. Mean age at onset was 49.3 years and mean duration of disease was 0.9 years. Genotyping revealed a common haplotype for the G41S allele. We provide the first evidence that the G41S mutation in Italy originates from a common founder. In addition, our findings strengthen the data reported previously and indicate that the G41S mutation is consistently associated with a uniform and dramatic, fast-progressing phenotype. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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90. Mutation analysis of the SPG4 gene in Italian patients with pure and complicated forms of spastic paraplegia
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Magariello, Angela, Muglia, Maria, Patitucci, Alessandra, Ungaro, Carmine, Mazzei, Rosalucia, Gabriele, Anna Lia, Sprovieri, Teresa, Citrigno, Luigi, Conforti, Francesca Luisa, Liguori, Maria, Gambardella, Antonio, Bono, Francesco, Piccoli, Tommaso, Patti, Francesco, Zappia, Mario, Mancuso, Michelangelo, Iemolo, Franco, and Quattrone, Aldo
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PARAPLEGIA , *PHENOTYPES , *COHORT analysis , *GENETIC mutation , *HUMAN chromosome abnormality diagnosis , *GENETICS - Abstract
Abstract: Mutations in the SPG4 gene are the most common causes of hereditary spastic paraplegia (HSP) accounting for up to 40% of autosomal dominant (AD) forms and 12–18% of sporadic cases. The phenotype associated with HSP due to mutations in the SPG4 gene tends to be pure. There is increasing evidence, however, of patients with complicated forms of spastic paraplegia in which SPG4 mutations were identified. A cohort of 38 unrelated Italian patients with spastic paraplegia, of which 24 had a clear dominant inheritance and 14 were apparently sporadic, were screened for mutations in the SPG4 gene. We identified 11 different mutations, six of which were novel (p.Glu143GlyfsX8, p.Tyr415X, p.Asp548Asn, c.1656_1664delinsTGACCT, c.1688-3C>G and c.*2G>T) and two exon deletions previously reported. The overall rate of SPG4 gene mutation in our patients was 36.8% (14/38); in AD-HSP we observed a mutation frequency of 45.8% (11/24), in sporadic cases the frequency was 21.4% (3/14). Furthermore, we found a mutational rate of 22.2% (2/9) and 41.4% (12/29) in the complicated and pure forms, respectively. The results underlie the importance of genetic testing in all affected individuals. [Copyright &y& Elsevier]
- Published
- 2010
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91. Coenzyme Q10 is frequently reduced in muscle of patients with mitochondrial myopathy
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Sacconi, Sabrina, Trevisson, Eva, Salviati, Leonardo, Aymé, Ségolène, Rigal, Odile, Garcia Redondo, Alberto, Mancuso, Michelangelo, Siciliano, Gabriele, Tonin, Paola, Angelini, Corrado, Auré, Karine, Lombès, Anne, and Desnuelle, Claude
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MUSCLE diseases , *UBIQUINONES , *MITOCHONDRIAL pathology , *GENETIC mutation , *MITOCHONDRIAL DNA abnormalities , *HIGH performance liquid chromatography , *CLINICAL trials , *PATIENTS - Abstract
Abstract: Coenzyme Q10 (CoQ10) deficiency has been associated with an increasing number of clinical phenotypes. Whereas primary CoQ10 defects are related to mutations in ubiquinone biosynthetic genes, which are now being unraveled, and respond well to CoQ10 supplementation, the etiologies, and clinical phenotypes related to secondary deficiencies are largely unknown. The purpose of this multicenter study was to evaluate the frequency of muscle CoQ10 deficiency in a cohort of 76 patients presenting with clinically heterogeneous mitochondrial phenotypes which included myopathy among their clinical features. A reliable diagnostic tool based on HPLC quantification was employed to measure muscle CoQ10 levels. A significant proportion of these patients (28 over 76) displayed CoQ10 deficiency that was clearly secondary in nine patients, who harbored a pathogenic mutation of mitochondrial DNA. This study provides a rationale for future therapeutic trials on the effect of CoQ10 supplementation in patients with mitochondrial diseases presenting with myopathy among clinical features. [Copyright &y& Elsevier]
- Published
- 2010
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92. Creutzfeldt-Jakob disease with E200K PRNP mutation: a case report and revision of the literature.
- Author
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Mancuso M, Siciliano G, Capellari S, Orsucci D, Moretti P, Fede GD, Suardi S, Strammiello R, Parchi P, Tagliavini F, Murri L, Mancuso, Michelangelo, Siciliano, Gabriele, Capellari, Sabina, Orsucci, Daniele, Moretti, Policarpo, Di Fede, Giuseppe, Suardi, Silvia, Strammiello, Rosaria, and Parchi, Piero
- Abstract
Creutzfeldt-Jakob disease (CJD) is typically characterized by rapidly progressive dementia and myoclonus, and it is caused by a conformational change of the prion protein. The heritable forms are associated with mutation in the gene encoding the prion protein (PRNP). We report a 63-year-old Italian woman harboring the E200K PRNP mutation. Electroencephalogram, cerebrospinal fluid analysis, PRNP gene sequencing, histopathologic examination, immunohistochemical studies, and Western blotting analysis confirmed the diagnosis of CJD. Pyramidal involvement was the first sign and the prominent clinical feature. Later on, she developed also myoclonus, ataxia, spastic tetraplegia, and at last dementia with akinetic mutism. Usually, signs of degeneration of the pyramidal tracts occur in a small number of patients as the disease advances. Our report supports the variability of the clinical expression of the E200K genetic CJD. Further studies are needed to understand the molecular basis underlying the phenotypic variability among patients carrying this mutation. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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93. Electron transfer mediators and other metabolites and cofactors in the treatment of mitochondrial dysfunction.
- Author
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Orsucci, Daniele, Filosto, Massimiliano, Siciliano, Gabriele, and Mancuso, Michelangelo
- Subjects
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MITOCHONDRIAL pathology , *PHOSPHORYLATION , *CHEMICAL reactions , *NEURODEGENERATION , *THERAPEUTICS , *REACTIVE oxygen species - Abstract
Mitochondrial disorders (MDs) are caused by impairment of the mitochondrial electron transport chain (ETC). The ETC is needed for oxidative phosphorylation, which provides the cell with the most efficient energy outcome in terms of ATP production. One of the pathogenic mechanisms of MDs is the accumulation of reactive oxygen species. Mitochondrial dysfunction and oxidative stress appear to also have a strong impact on the pathogenesis of neurodegenerative diseases and cancer. The treatment of MDs is still inadequate. Therapies that have been attempted include ETC cofactors, other metabolites secondarily decreased in MDs, antioxidants, and agents acting on lactic acidosis. However, the role of these dietary supplements in the treatment of the majority of MDs remains unclear. This article reviews the rationale for their use and their role in clinical practice in the context of MDs and other disorders involving mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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94. Mitochondrial disease and COVID-19: An international cohort study confirms risks and long-term outcomes.
- Author
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Pizzamiglio, Chiara, Jonvik, Hallgeir, Brady, Stefen, Chinnery, Patrick, Galàn, Lucía, Gorman, Grainne, Horga, Alejandro, Horvath, Rita, Janssen, Mirian, Lim, Albert, Mancuso, Michelangelo, Mcfarland, Robert, Molnar, Maria, Musumeci, Olimpia, Nesbitt, Victoria, Wladimir, Primiano, Guido, Santos, Ernestina, Servidei, Serenella, and Thomas, Rhys
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COHORT analysis , *MITOCHONDRIA - Published
- 2021
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95. Novel mitochondrial tRNALeu(CUN) transition and D4Z4 partial deletion in a patient with a facioscapulohumeral phenotype
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Filosto, Massimiliano, Tonin, Paola, Scarpelli, Mauro, Savio, Chiara, Greco, Francesca, Mancuso, Michelangelo, Vattemi, Gaetano, Govoni, Vittorio, Rizzuto, Nicolò, Tupler, Rossella, and Tomelleri, Giuliano
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DYSTROPHY , *GENES , *NEUROMUSCULAR diseases , *CLINICAL pathology - Abstract
Abstract: Point mutations in mtDNA-encoded tRNA genes frequently cause isolated myopathies but rarely cause the facioscapulohumeral phenotype. We report on a patient affected with chronic progressive weakness of facioscapulohumeral/peroneal muscles whose muscle biopsy showed a mitochondrial myopathy. mtDNA direct sequencing and RFLP analysis revealed a heteroplasmic transition T12313C which disrupts a conserved site in the TΨC stem of the tRNALeu(CUN) gene and fulfills the accepted criteria of pathogenicity. A partial deletion of the nuclear DNA D4Z4 region with residual repeat sizes of 25kb was also found in the patient and in her mother. This is the first reported case of mitochondrial myopathy/facioscapulohumeral muscular dystrophy (FSHD) “double trouble”. [Copyright &y& Elsevier]
- Published
- 2008
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96. Mitochondrial non-syndromic sensorineural hearing loss: a clinical, audiological and pathological study from Italy, and revision of the literature.
- Author
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BERRETTINI, Stefano, FORLI, Francesca, PASSETTI, Susanna, ROCCHI, Anna, POLLINA, Luca, CECCHETTI, Denise, MANCUSO, Michelangelo, and SICILIANO, Gabriele
- Subjects
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MITOCHONDRIAL DNA abnormalities , *EAR diseases , *SENSORINEURAL hearing loss , *AMINOGLYCOSIDES - Abstract
Over the last decade, a number of distinct mutations in the mtDNA (mitochondrial DNA) have been found to be associated with both syndromic and non-syndromic forms of hearing impairment. Their real incidence as a cause of deafness is poorly understood and generally underestimated. Among the known mtDNA mutations, the A1555G mutation in the 12S gene has been identified to be one of the most common genetic cause of deafness, and it has been described to be both associated to non-syndromic progressive SNHL (sensorineural hearing loss) and to aminoglycoside-induced SNHL. In the present study, we have investigated the presence of mtDNA alterations in patients affected by idiopathic non-syndromic SNHL, both familiar and sporadic, in order to evaluate the frequency of mtDNA alterations as a cause of deafness and to describe the audiological manifestations of mitochondrial nonsyndromic SNHL. In agreement with previous studies, we found the A1555G mutation to be responsible for a relevant percentage (5.4%) of cases affected with isolated idiopathic sensorineural hearing impairment. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
97. Bilateral striatal necrosis, dystonia and multiple mitochondrial DNA deletions: Case study and effect of deep brain stimulation.
- Author
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Aniello, Maria Stella, Martino, Davide, Petruzzella, Vittoria, Eleopra, Roberto, Mancuso, Michelangelo, Dell'Aglio, Rosa, Cavallo, Michele, Siciliano, Gabriele, and Defazio, Giovanni
- Abstract
Bilateral striatal necrosis (BSN) is relatively rare and has been related to a wide array of causes, including nuclear and mitochondrial DNA mutations. We report the clinical vignette of a patient with a 37 years-history of generalized dystonia secondary to BSN associated with multiple mitochondrial DNA deletions of undefined origin. Globus pallidus interna deep brain stimulation produced sustained benefit, with predominant improvements in disability. © 2007 Movement Disorder Society [ABSTRACT FROM AUTHOR]
- Published
- 2008
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98. A high-dose bortezomib neuropathy with sensory ataxia and myelin involvement
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Filosto, Massimiliano, Rossi, Giuseppe, Pelizzari, Anna Maria, Buzio, Serena, Tentorio, Marta, Broglio, Laura, Mancuso, Michelangelo, Rinaldi, Marianna, Scarpelli, Mauro, and Padovani, Alessandro
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NEUROPATHY , *ALTERNATIVE medicine , *MOVEMENT disorders , *ATAXIA - Abstract
Abstract: Bortezomib, a proteasome inhibitor used in the treatment of multiple myeloma, is known to induce an axonal, dose-dependent neuropathy clinically characterized by pain, paresthesias, burning dysesthesias and numbness. In this study, we describe a patient treated with high-dose bortezomib whose main clinical feature was severe sensory ataxia. Electrodiagnostic studies showed, other than axonal changes, myelin involvement. [Copyright &y& Elsevier]
- Published
- 2007
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99. Novel spastin (SPG4) mutations in Italian patients with hereditary spastic paraplegia
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Magariello, Angela, Muglia, Maria, Patitucci, Alessandra, Mazzei, Rosalucia, Conforti, Francesca Luisa, Gabriele, Anna Lia, Sprovieri, Teresa, Ungaro, Carmine, Gambardella, Antonio, Mancuso, Michelangelo, Siciliano, Gabriele, Branca, Damiano, Aguglia, Umberto, de Angelis, Maria Vittoria, Longo, Katia, and Quattrone, Aldo
- Subjects
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LEG diseases , *GENETICS , *PARALYSIS , *GENETIC mutation - Abstract
Abstract: Spastic paraplegia type 4 is caused by mutations in the gene that encodes spastin (SPG4), a member of the AAA protein family. A cohort of 34 unrelated Italian patients with pure spastic paraplegia, of which 18 displayed autosomal dominant inheritance and 16 were apparently sporadic, were screened for mutations in the SPG4 gene by denaturing high performance liquid chromatography. We identified a previously reported mutation in a sporadic patient with pure hereditary spastic paraplegia. We also identified eight unrelated patients with pure autosomal dominant hereditary spastic paraplegia carrying five novel mutations in the SPG4 gene (one missense mutation, c.1304 C>T; one nonsense mutation, c.807C>A; two frameshift mutations, c.1281dupT, c.1514_1515insATA; and one splicing mutation, c.1322-2A>C). The frequency for SPG4 mutations detected in autosomal dominant hereditary spastic paraplegia was 44.4%. This study contributes to expand the spectrum of SPG4 mutations in Italian population. [Copyright &y& Elsevier]
- Published
- 2006
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100. Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer’s disease
- Author
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Bosetti, Francesca, Brizzi, Francesca, Barogi, Silvia, Mancuso, Michelangelo, Siciliano, Gabriele, Tendi, Elisabetta A., Murri, Luigi, Rapoport, Stanley I., and Solaini, Giancarlo
- Subjects
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ALZHEIMER'S disease , *MITOCHONDRIAL pathology - Abstract
Evidence suggests that mitochondrial dysfunction is prominent in Alzheimer’s disease (AD). A failure of one or more of the mitochondrial electron transport chain enzymes or of F1F0-ATPase (ATP synthase) could compromise brain energy stores, generate damaging reactive oxygen species (ROS), and lead to neuronal death. In the present study, cytochrome c oxidase (COX) and F1F0-ATPase activities of isolated mitochondria from platelets and postmortem motor cortex and hippocampus from AD patients and age-matched control subjects were assayed. Compared with controls, COX activity was decreased significantly in platelets (-30%, P < 0.01, n = 20) and hippocampus (-35 to -40%, P < 0.05, n = 6), but not in motor cortex from the AD patients. In contrast, in AD platelets and brain tissues, F1F0-ATP hydrolysis activity was not significantly changed. Moreover, the ATP synthesis rate was similar in mitochondria of platelets from AD patients and controls. These results demonstrate that COX but not F1F0-ATPase is a mitochondrial target in AD, in both a brain association area and in platelets. A reduced COX activity may make the tissue vulnerable to excitotoxicity or reduced oxygen availability. Abbreviations: Aβ: amyloid beta; AD: Alzheimer’s disease; COX: cytochrome oxidase; OS-ATPase: oligomycin-sensitive ATPase; ROS: reactive oxygen species. [Copyright &y& Elsevier]
- Published
- 2002
- Full Text
- View/download PDF
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