EDUARDO DE PAULA ESTEPHAN
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
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- A case of mitochondrial DNA depletion syndrome type 11-expanding the genotype and phenotype(2023) ROCHA, Emanuelle Bianchi da Silva; RODRIGUES, Ketteny de Lima; MONTOURO, Laura Alonso Matheus; COELHO, erica Nogueira; KOUYOUMDJIAN, Joao Aris; KOK, Fernando; NOBREGA, Paulo Ribeiro; GRACA, Carla Renata; MORITA, Maria da Penha Ananias; ESTEPHAN, Eduardo de PaulaMitochondrial DNA depletion syndrome type 11 (MTDPS11) is caused by pathogenic variants in MGME1 gene. We report a woman, 40-year-old, who presented slow progressive drop eyelid at 11-year old with, learning difficulty and frequent falls. Phisical examination revealed: mild scoliosis, elbow hyperextensibility, flat feet, chronic progressive external ophthalmoplegia with upper eyelid ptosis, diffuse hypotonia, and weakness of arm abduction and neck flexion. Investigation evidenced mild serum creatine kinase increase and glucose intolerance; second-degree atrioventricular block; mild mixed type respiratory disorder and atrophy and granular appearance of the retinal pigment epithelium. Brain magnetic resonance showed cerebellar atrophy. Muscle biopsy was compatible with mitochondrial myopathy. Genetic panel revealed a homozygous pathogenic variant in the MGME1 gene, consistent with MTDPS11 (c.862C > T; p.Gln288 *). This case of MTDPS11 can contribute to the phenotypic characterization of this ultra-rare mitochondrial disorder, presenting milder respiratory and nutritional involvement than the previously reported cases, with possible additional features.(c) 2023 Elsevier B.V. All rights reserved.
- Myasthenia Gravis Related to Thymic Carcinoma: A Case Study(2020) LOPES, Daniel Thomas Pereira; GOMES, Samila Marissa Pinheiro; SIQUEIRA, Sheila Aparecida Coelho; FRASSETTO, Fernando Pereira; SAMPAIO, Pedro Henrique Martins Arruda; MORENO, Cristiane Araujo Martins; ROCHA, Maria Sheila Guimaraes; ESTEPHAN, Eduardo PaulaMyasthenia gravis and thymoma are often presented in association with similar to 10% of myasthenic cases having concomitant thymoma. Thymic carcinoma is one of the rarest/aggressive human epithelial tumors and has no correlation with myasthenia gravis hitherto. Here is provided a clinical case and review of literature on a very rare association of thymic carcinoma (with no sign of thymoma) and myasthenia gravis (antiacetylcholine receptor antibody positive). Two years after thymectomy, clinical evolution was satisfactory. This clinical case elicits hypothesis that thymic carcinoma may be related with myasthenia gravis, what may have good prognostic from oncologic and neurologic perspectives.
- Myasthenia Gravis and COVID-19: Clinical Characteristics and Outcomes(2020) CAMELO-FILHO, Antonio E.; SILVA, Andre M. S.; ESTEPHAN, Eduardo P.; ZAMBON, Antonio A.; MENDONCA, Rodrigo H.; SOUZA, Paulo V. S.; PINTO, Wladimir B. V. R.; OLIVEIRA, Acary S. B.; DANGONI-FILHO, Iron; POUZA, Ana F. P.; VALERIO, Berenice C. O.; ZANOTELI, EdmarMyasthenia gravis (MG), an autoimmune neuromuscular disorder, may be a risk factor for severe COVID-19. We conducted an observational retrospective study with 15 consecutive adult MG patients admitted with COVID-19 at four hospitals in Sao Paulo, Brazil. Most patients with MG hospitalized for COVID-19 had severe courses of the disease: 87% were admitted in the intensive care unit, 73% needed mechanical ventilation, and 30% died. Immunoglobulin use and the plasma exchange procedure were safe. Immunosuppressive therapy seems to be associated with better outcomes, as it might play a protective role.
- Mutations in PTPN11 could lead to a congenital myasthenic syndrome phenotype: a Noonan syndrome case series(2024) PUGLIESE, Alessia; MARINA, Adela Della; ESTEPHAN, Eduardo de Paula; ZANOTELI, Edmar; ROOS, Andreas; SCHARA-SCHMIDT, Ulrike; HENTSCHEL, Andreas; AZUMA, Yoshiteru; TOPF, Ana; THOMPSON, Rachel; POLAVARAPU, Kiran; LOCHMUELLER, HannsThe RASopathies are a group of genetic rare diseases caused by mutations affecting genes involved in the RAS/MAPK (RAS-mitogen activated protein kinase) pathway. Among them, PTPN11 pathogenic variants are responsible for approximately 50% of Noonan syndrome (NS) cases and, albeit to a lesser extent, of Leopard syndrome (LPRD1), which present a few overlapping clinical features, such as facial dysmorphism, developmental delay, cardiac defects, and skeletal deformities. Motor impairment and decreased muscle strength have been recently reported. The etiology of the muscle involvement in these disorders is still not clear but probably multifactorial, considering the role of the RAS/MAPK pathway in skeletal muscle development and Acetylcholine Receptors (AChR) clustering at the neuromuscular junction (NMJ). We report, herein, four unrelated children carrying three different heterozygous mutations in the PTPN11 gene. Intriguingly, their phenotypic features first led to a clinical suspicion of congenital myasthenic syndrome (CMS), due to exercise-induced fatigability with a variable degree of muscle weakness, and serum proteomic profiling compatible with a NMJ defect. Moreover, muscle fatigue improved after treatment with CMS-specific medication. Although the link between PTPN11 gene and neuromuscular transmission is unconfirmed, an increasing number of patients with RASopathies are affected by muscle weakness and fatigability. Hence, NS or LPDR1 should be considered in children with suspected CMS but negative genetic workup for known CMS genes or additional symptoms indicative of NS, such as facial dysmorphism or intellectual disability.
- Clinical and molecular findings in a cohort of ANO5-related myopathy(2019) SILVA, Andre M. S.; COIMBRA-NETO, Antonio R.; SOUZA, Paulo Victor S.; WINCKLER, Pablo B.; GONCALVES, Marcus V. M.; CAVALCANTI, Eduardo B. U.; CARVALHO, Alzira A. D. S.; SOBREIRE, Claudia F. D. R.; CAMELO, Clara G.; MENDONCA, Rodrigo D. H.; ESTEPHAN, Eduardo D. P.; REED, Umbertina C.; MACHADO-COSTA, Marcela C.; DOURADO-JUNIOR, Mario E. T.; PEREIRA, Vanessa C.; CRUZEIRO, Marcelo M.; HELITO, Paulo V. P.; AIVAZOGLOU, Lais U.; CAMARGO, Leonardo V. D.; GOMES, Hudson H.; CAMARGO, Amaro J. S. D.; PINTO, Wladimir B. V. D. R.; BADIA, Bruno M. L.; LIBARDI, Luiz H.; YANAGIURA, Mario T.; OLIVEIRA, Acary S. B.; NUCCI, Anamarli; SAUTE, Jonas A. M.; FRANCA-JUNIOR, Marcondes C.; ZANOTELI, EdmarObjective ANO5-related myopathy is an important cause of limb-girdle muscular dystrophy (LGMD) and hyperCKemia. The main descriptions have emerged from European cohorts, and the burden of the disease worldwide is unclear. We provide a detailed characterization of a large Brazilian cohort of ANO5 patients. Methods A national cross-sectional study was conducted to describe clinical, histopathological, radiological, and molecular features of patients carrying recessive variants in ANO5. Correlation of clinical and genetic characteristics with different phenotypes was studied. Results Thirty-seven patients from 34 nonrelated families with recessive mutations of ANO5 were identified. The most common phenotype was LGMD, observed in 25 (67.5%) patients, followed by pseudometabolic presentation in 7 (18.9%) patients, isolated asymptomatic hyperCKemia in 4 (10.8%) patients, and distal myopathy in a single patient. Nine patients presented axial involvement, including one patient with isolated axial weakness. The most affected muscles according to MRI were the semimembranosus and gastrocnemius, but paraspinal and abdominal muscles, when studied, were involved in most patients. Fourteen variants in ANO5 were identified, and the c.191dupA was present in 19 (56%) families. Sex, years of disease, and the presence of loss-of-function variants were not associated with specific phenotypes. Interpretation We present the largest series of anoctaminopathy outside Europe. The most common European founder mutation c.191dupA was very frequent in our population. Gender, disease duration, and genotype did not determine the phenotype.
- Electrophysiological evaluation of the neuromuscular junction: a brief review(2023) KOUYOUMDJIAN, Joao Aris; ESTEPHAN, Eduardo de PaulaThe nerve terminal and muscle membrane compose the neuromuscular junction. After opening the voltage-gated calcium channels, action potentials from the motor axons provoke a cascade for the acetylcholine release from synaptic vesicles to the synaptic cleft, where it binds to its receptor at the muscle membrane for depolarization. Low amplitude compound muscle action potential typically presents in presynaptic disorders, increasing by more than 100% after a 10-second effort in the Lambert-Eaton myasthenic syndrome and less in botulism. Needle electromyography may show myopathic motor unit action potentials and morphological instability ('' jiggle '') due to impulse blocking. Low-frequency repetitive nerve stimulation (RNS) is helpful in postsynaptic disorders, such as myasthenia gravis and most congenital myasthenic syndromes, where the number of functioning acetylcholine receptors is reduced. Low-frequency RNS with a decrement > 10% is abnormal when comparing the 4th to the first compound muscle action potential amplitude. High-frequency RNS is helpful in presynaptic disorders like Lambert-Eaton myasthenic syndrome, botulism, and some rare congenital myasthenic syndromes. The high-frequency RNS releases more calcium, increasing the acetylcholine with a compound muscle action potential increment. Concentric needle records apparent single-fiber action potentials (spikes). A voluntary activation measures the jitter between spikes from two endplates. An electrical activation measures the jitter of one spike (one endplate). The jitter is the most sensitive test for detecting a neuromuscular junction dysfunction. Most neuromuscular junction disorders are responsive to treatment.