EDMAR ZANOTELI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Neurologia, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/15 - Laboratório de Investigação em Neurologia, Hospital das Clínicas, Faculdade de Medicina
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/15 - Laboratório de Investigação em Neurologia, Hospital das Clínicas, Faculdade de Medicina
184 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 184
- Clinical and genetic spectrum of a large cohort of patients with delta-sarcoglycan muscular dystrophy(2022) ALONSO-PEREZ, Jorge; GONZALEZ-QUEREDA, Lidia; BRUNO, Claudio; PANICUCCI, Chiara; ALAVI, Afagh; NAFISSI, Shahriar; NILIPOUR, Yalda; ZANOTELI, Edmar; ISIHI, Lucas Michielon de Augusto; MELEGH, Bela; HADZSIEV, Kinga; MUELAS, Nuria; VILCHEZ, Juan J.; DOURADO, Mario Emilio; KADEM, Naz; KUTLUK, Gultekin; UMAIR, Muhammad; YOUNUS, Muhammad; PEGORANO, Elena; BELLO, Luca; CRAWFORD, Thomas O.; SUAREZ-CALVET, Xavier; TOPF, Ana; GUGLIERI, Michela; MARINI-BETTOLO, Chiara; GALLANO, Pia; STRAUB, Volker; DIAZ-MANERA, JordiSarcoglycanopathies include four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. Delta-sarcoglycanopathy (LGMDR6) is the least frequent and is considered an ultra-rare disease. Our aim was to characterize the clinical and genetic spectrum of a large international cohort of LGMDR6 patients and to investigate whether or not genetic or protein expression data could predict a disease's severity. This is a retrospective study collecting demographic, genetic, clinical and histological data of patients with genetically confirmed LGMDR6 including protein expression data from muscle biopsies. We contacted 128 paediatric and adult neuromuscular units around the world that reviewed genetic data of patients with a clinical diagnosis of a neuromuscular disorder. We identified 30 patients with a confirmed diagnosis of LGMDR6 of which 23 patients were included in this study. Eighty-seven per cent of the patients had consanguineous parents. Ninety-one per cent of the patients were symptomatic at the time of the analysis. Proximal muscle weakness of the upper and lower limbs was the most common presenting symptom. Distal muscle weakness was observed early over the course of the disease in 56.5% of the patients. Cardiac involvement was reported in five patients (21.7%) and four patients (17.4%) required non-invasive ventilation. Sixty per cent of patients were wheelchair-bound since early teens (median age of 12.0 years). Patients with absent expression of the sarcoglycan complex on muscle biopsy had a significant earlier onset of symptoms and an earlier age of loss of ambulation compared to patients with residual protein expression. This study confirmed that delta-sarcoglycanopathy is an ultra-rare neuromuscular condition and described the clinical and molecular characteristics of the largest yet-reported collected cohort of patients. Our results showed that this is a very severe and quickly progressive disease characterized by generalized muscle weakness affecting predominantly proximal and distal muscles of the limbs. Similar to other forms of sarcoglycanopathies, the severity and rate of progressive weakness correlates inversely with the abundance of protein on muscle biopsy.
- Inflammatory myopathies: an update for neurologists(2022) SILVA, Andre Macedo Serafim; CAMPOS, Eliene Dutra; ZANOTELI, EdmarIdiopathic inflammatory myopathies (IIM) are a heterogenous group of treatable myopathies. Patients present mainly to the rheumatologist and neurologists, complaining of acute or subacute onset of proximal weakness. Extramuscular manifestations may occur, including involvement of the lungs, skin, and joints. Classically, the diagnosis used to be made based on the creatine kinase level increase, abnormalities in electroneuromyography and presence of inflammatory infiltrates in the muscle biopsy. Recently, the importance of autoantibodies has increased, and now they may be identified in more than half of IIM patients. The continuous clinicoseropathological improvement in IIM knowledge has changed the way we see these patients and how we classify them. In the past, only polymyositis, dermatomyositis and inclusion body myopathy were described. Currently, immune-mediated necrotizing myopathy, overlap myositis and antisynthetase syndrome have been considered the most common forms of IIM in clinical practice, increasing the spectrum of classification. Patients previously considered to have polymyositis, in fact have these other forms of seropositive IIM. In this article, we reviewed the new concepts of classification, a practical way to make the diagnosis and how to plan the treatment of patients suffering from IIM.
- Abnormal myosin post-translational modifications and ATP turnover time associated with human congenital myopathy-related RYR1 mutations(2023) SONNE, Alexander; ANTONOVIC, Anna Katarina; MELHEDEGAARD, Elise; AKTER, Fariha; ANDERSEN, Jesper L.; JUNGBLUTH, Heinz; WITTING, Nanna; VISSING, John; ZANOTELI, Edmar; FORNILI, Arianna; OCHALA, JulienAimConditions related to mutations in the gene encoding the skeletal muscle ryanodine receptor 1 (RYR1) are genetic muscle disorders and include congenital myopathies with permanent weakness, as well as episodic phenotypes such as rhabdomyolysis/myalgia. Although RYR1 dysfunction is the primary mechanism in RYR1-related disorders, other downstream pathogenic events are less well understood and may include a secondary remodeling of major contractile proteins. Hence, in the present study, we aimed to investigate whether congenital myopathy-related RYR1 mutations alter the regulation of the most abundant contractile protein, myosin. MethodsWe used skeletal muscle tissues from five patients with RYR1-related congenital myopathy and compared those with five controls and five patients with RYR1-related rhabdomyolysis/myalgia. We then defined post-translational modifications on myosin heavy chains (MyHCs) using LC/MS. In parallel, we determined myosin relaxed states using Mant-ATP chase experiments and performed molecular dynamics (MD) simulations. ResultsLC/MS revealed two additional phosphorylations (Thr1309-P and Ser1362-P) and one acetylation (Lys1410-Ac) on the & beta;/slow MyHC of patients with congenital myopathy. This method also identified six acetylations that were lacking on MyHC type IIa of these patients (Lys35-Ac, Lys663-Ac, Lys763-Ac, Lys1171-Ac, Lys1360-Ac, and Lys1733-Ac). MD simulations suggest that modifying myosin Ser1362 impacts the protein structure and dynamics. Finally, Mant-ATP chase experiments showed a faster ATP turnover time of myosin heads in the disordered-relaxed conformation. ConclusionsAltogether, our results suggest that RYR1 mutations have secondary negative consequences on myosin structure and function, likely contributing to the congenital myopathic phenotype.
conferenceObject ATYPICAL AND UNCLASSIFIED CASES OF INFLAMMATORY MYOPATHIES(2018) SILVA, A. M. S.; MENDONCA, R. H.; ZANOTELI, E.- Hypercontractile congenital muscle stiffness(2018) CAMELO, C.; SILVA, A. Da; REED, U.; BONNEMANN, C.; ZANOTELI, E.
conferenceObject RAINBOWFISH: Preliminary Efficacy and Safety Data in Risdiplam-Treated Infants with Presymptomatic SMA(2022) FINKEL, Richard S.; FARRAR, Michelle A.; VLODAVETS, Dmitry; SERVAIS, Laurent; ZANOTELI, Edmar; AL-MUHAIZEA, Mohammad; NELSON, Leslie; PRUFER, Alexandra; WANG, Yi; FISHER, Carolyn; GERBER, Marianne; GORNI, Ksenija; KLETZL, Heidemarie; PALFREEMAN, Laura; SCALCO, Renata; BERTINI, Enrico- Inclusion-body myositis: a difficult diagnosis?(2014) CORREIA, Carolina da Cunha; MAGALHÃES, Maria Clara de Oliveira; BARBOSA, Pedro Lucas de Mendonça; CAMPOS, Eliene Dutra; ZANOTELI, EdmarSporadic inclusion-body myositis (IBM) is the most common myopathy in individuals over 55 years of age. However, in many cases, the diagnosis is neglected. Its main findings include progressive muscle weakness, normal or low levels of serum creatine kinase, and the absence of a response to immunosuppression. Muscle biopsy shows inflammatory reaction in association with degenerative changes of the muscle fibers. We report a typical case of IBM, in which diagnosis was possible only after three muscle biopsies. The challenges to confirm histological diagnosis and the caution to avoid repeating tests are discussed.
- Whole-Body MRI in Limb Girdle Muscular Dystrophy Type R1/2A: Correlation With Clinical Scores(2022) AIVAZOGLOU, Lais U.; GUIMARAES, Julio B.; COSTA, Maria Alice F.; AIHARA, Andre Yui; CARDOSO, Fabiano N.; PINTO, Wladimir B. V. De R.; SOUZA, Paulo Victor S. de; SILVA, Andre M. S. da; ZANOTELI, Edmar; OLIVEIRA, Acary S. B.; CARVALHO, Alzira A. S.; FERNANDES, Artur Da R. C.Introduction/Aim The most common limb girdle muscular dystrophy (LGMD) worldwide is LGMD type R1 (LGMDR1). The aim of this study was to correlate the MRI findings with functional scores and to describe the whole-body MRI (WBMRI) pattern in a LGMDR1 Brazilian cohort. Methods LGMDR1 patients under follow-up in three centers were referred for the study. Clinical data were collected and a functional evaluation was performed, consisting of Gardner-Medwin and Walton (GMW) and Brooke scales. All patients underwent a WBMRI study (1.5T) with axial T1 and STIR images. Fifty-one muscles were semiquantitatively assessed regarding fatty infiltration and muscle edema. Results The study group consisted of 18 patients. The highest fatty infiltration scores involved the serratus anterior, biceps femoris long head, adductor magnus, and lumbar erector spinae. There was a latero-medial and caudo-cranial descending gradient of involvement of the paravertebral muscles, with erector spinae being significantly more affected than the transversospinalis muscles (p < 0.05). A striped appearance that has been dubbed the ""pseudocollagen sign"" was present in 72% of the patients. There was a positive correlation between the MRI score and GMW (Rho:0.83) and Brooke (Rho:0.53) scores. Discussion WBMRI in LGMDR1 allows a global patient evaluation including involvement of the paraspinal muscles, usually an underestimated feature in the clinical and imaging study of myopathies. Knowledge of the WBMRI pattern of LGMDR1 involvement can be useful in the diagnostic approach and in future studies to identify the best target muscles to serve as outcome measures in clinical trials.
- Clinical Manifestation of Nebulin-Associated Nemaline Myopathy(2023) MORENO, Cristiane Araujo Martins; ARTILHEIRO, Mariana Cunha; FONSECA, Alulin Tacio Quadros Santos Monteiro; CAMELO, Clara Gontijo; MEDEIROS, Gisele Chagas de; SASSI, Fernanda Chiarion; ANDRADE, Claudia Regina Furquim de; DONKERVOORT, Sandra; SILVA, Andre Macedo Serafim; DALFIOR-JUNIOR, Luiz; ABATH-NETO, Osorio Lopes; REED, Umbertina Conti; BOENNEMANN, Carsten; ZANOTELI, EdmarBackground and ObjectivesNemaline myopathy (NM) is a genetically heterogeneous inherited myopathy related with at least 12 genes, whereas pathogenic variants in NEB gene are the most common genetic cause. The clinical spectrum of NM caused by NEB pathogenic variants (NM-NEB) is very broad, ranging from mild to severe presentations manifesting with generalized weakness, as well as respiratory and bulbar involvement. There is currently not enough data regarding the progression of the disease. In this study, we present a genotypic and phenotypic spectrum of 33 patients with NM caused by NEB variants (NM-NEB) classified according to age groups and the use of ventilatory support. We focused on interventional support, genotype-phenotype correlation, and association between respiratory, bulbar, and motor systems in groups of patients stratified by age and by the use of ventilatory support (VS). MethodsClinical and genetic data from patients with NM-NEB followed up in one specialized center were collected through regular consultations. Patients were evaluated regarding motor, bulbar, and respiratory functions. ResultsThirty-three patients with NM-NEB were evaluated consisting of 15 females and 18 males with an average age of 18 (+/- 12) years and a median of 17 (+/- 11) years. 32% of patients with NM-NEB used a G tube, 35% were not able to walk without support, and 55% needed VS. Scoliosis and dysphagia were more common among patients who used VS. Described for the first time, half of the patients presented tongue atrophy in a triple furrow pattern, and the presence of the atrophy was associated with dysphagia. Comparing the patients grouped by age, we found that, proportionally, older patients had more scoliosis and respiratory dysfunction than younger groups, suggesting the progression of the disease in these domains. In addition to that, we showed that VS use was associated with scoliosis and dysphagia. DiscussionNM-NEB is a very debilitating disease. There is an association between scoliosis and respiratory dysfunction while patients using VS have more often scoliosis than the no-VS group. Triple furrow tongue atrophy is a novel and frequent finding, which is directly associated with dysphagia. Grouping patients by age suggested disease stability in motor and swallow function, but a progression in respiratory dysfunction and skeletal deformities. All observations are relevant in the management care of patients with NM.
- Air stacking: effects on pulmonary function in patients with spinal muscular atrophy and in patients with congenital muscular dystrophy(2014) MARQUES, Tanyse Bahia Carvalho; NEVES, Juliana de Carvalho; PORTES, Leslie Andrews; SALGE, Joao Marcos; ZANOTELI, Edmar; REED, Umbertina ContiObjective: Respiratory complications are the main causes of morbidity and mortality in patients with neuromuscular disease (NMD). The objectives of this study were to determine the effects that routine daily home air-stacking maneuvers have on pulmonary function in patients with spinal muscular atrophy (SMA) and in patients with congenital muscular dystrophy (CMD), as well as to identify associations between spinal deformities and the effects of the maneuvers. Methods: Eighteen NMD patients (ten with CMD and eight with SMA) were submitted to routine daily air-stacking maneuvers at home with manual resuscitators for four to six months, undergoing pulmonary function tests before and after that period. The pulmonary function tests included measurements of FVC; PEF; maximum insufflation capacity (MIC); and assisted and unassisted peak cough flow (APCF and UPCF, respectively) with insufflations. Results: After the use of home air-stacking maneuvers, there were improvements in the APCF and UPCF. In the patients without scoliosis, there was also a significant increase in FVC. When comparing patients with and without scoliosis, the increases in APCF and UPCF were more pronounced in those without scoliosis. Conclusions: Routine daily air-stacking maneuvers with a manual resuscitator appear to increase UPCF and APCF in patients with NMD, especially in those without scoliosis.