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
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
- Myasthenia gravis in clinical practice(2022) ESTEPHAN, Eduardo de Paula; BAIMA, Jose Pedro Soares; ZAMBON, Antonio AlbertoBackground: Myasthenia gravis is largely a treatable disease, but it can result in significant morbidity and even mortality, which can usually be avoided, or at least mitigated, with timely diagnosis and appropriate treatment of the disease. Objective: This review aims to summarize the main practical aspects of the diagnostic approach, treatment and care of myasthenic patients. Methods: The authors performed a non-systematic critical review summarizing the main practical aspects of myasthenia gravis. Results: Most patients with myasthenia have autoantibodies targeted at acetylcholine receptors or, less commonly, muscle-specific kinase - MuSK. Electrophysiology plays an important role in the diagnosis of neuromuscular junction dysfunction. The central clinical manifestation of myasthenia gravis is fatigable muscle weakness, which can affect eye, bulbar, respiratory, and limb muscles. With rare exceptions, patients have a good response to symptomatic treatment, but corticosteroids and/or immunosuppressants are usually also necessary to obtain good control of the manifestations of the disease.Conclusion: Knowledge of the peculiar aspects of their clinical and electrophysiological presentations is important for the diagnosis. Likewise, specific treatment and response time to each drug are crucial for proper care.
- Electrophysiological study of neuromuscular junction in congenital myasthenic syndromes, congenital myopathies, and chronic progressive external ophthalmoplegia(2020) CALDAS, Vitor Marques; HEISE, Carlos Otto; KOUYOUMDJIAN, Joao Aris; ZAMBON, Antonio Alberto; SILVA, Andre Macedo Serafim; ESTEPHAN, Eduardo de Paula; ZANOTELI, EdmarThis study was designed to analyze the sensitivity, specificity, and accuracy of jitter parameters combined with repetitive nerve stimulation (RNS) in congenital myasthenic syndrome (CMS), chronic progressive external ophthalmoplegia (CPEO), and congenital myopathies (CM). Jitter was obtained with a concentric needle electrode during voluntary activation of the Orbicularis Oculi muscle in CMS ( n = 21), CPEO ( n = 20), and CM ( n = 18) patients and in controls ( n = 14). RNS (3 Hz) was performed in six different muscles for all patients ( Abductor Digiti Minimi, Tibialis Anterior, upper Trapezius, Deltoideus, Orbicularis Oculi, and Nasalis). RNS was abnormal in 90.5% of CMS patients and in only one CM patient. Jitter was abnormal in 95.2% of CMS, 20% of CPEO, and 11.1% of CM patients. No patient with CPEO or CM presented a mean jitter higher than 53.6 mu s or more than 30% abnormal individual jitter (> 45 mu s). No patient with CPEO or CM and mild abnormal jitter values presented an abnormal decrement. Jitter and RNS assessment are valuable tools for diagnosing neuromuscular transmission abnormalities in CMS patients. A mean jitter value above 53.6 mu s or the presence of more than 30% abnormal individual jitter (> 45 mu s) strongly suggests CMS compared with CPEO and CM.
conferenceObject PROPOSING OF A LESS COSTLY STRATEGY FOR MOLECULAR DIAGNOSIS OF CONGENITAL MYASTHENIC SYNDROME IN BRAZIL.(2018) ESTEPHAN, E. P.; SILVA, M. A. S.; ZAMBON, A. A.; REED, U. C.; TOPF, A.; LOCHMUELLER, H.; ZANOTELI, E.- The p.N88K mutation in the RAPSN gene in Brazilian patients with congenital myasthenic syndrome(2018) ESTEPHAN, E.; ZAMBON, A.; MARCHIORI, P.; SILVA, A.; MORENO, C.; REED, U.; TOPF, A.; LOCHMUELLER, H.; ZANOTELIL, E.
- 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.
- A common CHRNE mutation in Brazilian patients with congenital myasthenic syndrome(2018) ESTEPHAN, Eduardo de Paula; SOBREIRA, Claudia Ferreira da Rosa; SANTOS, Andre Cleriston Jose dos; TOMASELLI, Pedro Jose; MARQUES JR., Wilson; ORTEGA, Roberta Paiva Magalhes; COSTA, Marcela Camara Machado; SILVA, Andre Macedo Serafim da; MENDONCA, Rodrigo Holanda; CALDAS, Vitor Marques; ZAMBON, Antonio Alberto; ABATH NETO, Osorio; MARCHIORI, Paulo Euripedes; HEISE, Carlos Otto; REED, Umbertina Conti; AZUMA, Yoshiteru; TOPF, Ana; LOCHMULLER, Hanns; ZANOTELI, EdmarThe most common causes of congenital myasthenic syndromes (CMS) are CHRNE mutations, and some pathogenic allelic variants in this gene are especially frequent in certain ethnic groups. In the southern region of Brazil, a study found the c.130dupG CHRNE mutation in up to 33% of families with CMS. Here, we aimed to verify the frequency of this mutation among individuals with CMS in a larger cohort of CMS patients from different areas of Brazil and to characterize clinical features of these patients. Eighty-four patients with CMS, from 72 families, were clinically evaluated and submitted to direct sequencing of the exon 2 of CHRNE. The c.130dupG mutation was found in 32 patients (23 families), with 26 patients (19 families, 26.3%) in homozygosis, confirming its high prevalence in different regions of Brazil. Among the homozygous patients, the following characteristics were frequent: onset of symptoms before 2 years of age (92.3%), little functional restriction (92.3%), fluctuating symptoms (100%), ocular muscle impairment (96.1%), ptosis (100%), limb weakness (88.4%), response to pyridostigmine (100%), facial involvement (77%), and bulbar symptoms (70.8%). The pretest probability of finding at least one allele harbouring the c.130dupG mutation was 38.1%. Selecting only patients with impaired eye movement together with limb weakness and improvement with pyridostigmine, the probability increases to 72.2%. This clinical pre-selection of patients is likely a useful tool for regions where CHRNE mutations have a founder effect. In conclusion, the CHRNE mutation c.130dupG leads to fairly benign natural course of the disease with relative homogeneity.
- Clinical variability of early-onset congenital myasthenic syndrome due to biallelic RAPSN mutations in Brazil(2018) ESTEPHAN, Eduardo de Paula; ZAMBON, Antonio Alberto; MARCHIORI, Paulo Euripedes; SILVA, Andre Macedo Serafim da; CALDAS, Vitor Marques; MORENO, Cristiane Araujo Martins; REED, Umbertina Conti; HORVATH, Rita; TOPF, Ana; LOCHMUELLER, Hanns; ZANOTELI, EdmarMutations in RAPSN are an important cause of congenital myasthenic syndrome (CMS), leading to endplate acetylcholine receptor deficiency. We present three RAPSN earlyonset CMS patients (from a Brazilian cohort of 61 CMS patients). Patient 1 and patient 2 harbor the mutation p.N88K in homozygosity, while patient 3 harbors p.N88K in compound heterozygosity with another pathogenic variant (p.V165M; c.493G > A). At onset, patient 3 presented with more severe symptoms compared to the other two, showing generalized weakness and repeated episodes of respiratory failure in the first years of life. During adolescence, she became gradually less symptomatic and does not require medication anymore, presenting better long-term outcomes than patients 1 and 2. This case series illustrates the variability of RAPSN earlyonset CMS, with patient 3, despite severe onset, revealing an almost complete reversal of myasthenic symptoms, not limited to apneic episodes. Moreover, it suggests that RAPSN CMS may be underdiagnosed in nonEuropean countries.
- Congenital myasthenic syndrome: Correlation between clinical features and molecular diagnosis(2022) ESTEPHAN, Eduardo P.; ZAMBON, Antonio A.; THOMPSON, Rachel; POLAVARAPU, Kiran; JOMAA, Danny; TOPF, Ana; HELITO, Paulo V. P.; HEISE, Carlos O.; MORENO, Cristiane A. M.; SILVA, Andre M. S.; KOUYOUMDJIAN, Joao A.; MORITA, Maria da Penha; REED, Umbertina C.; LOCHMULLER, Hanns; ZANOTELI, EdmarObjectives To present phenotype features of a large cohort of congenital myasthenic syndromes (CMS) and correlate them with their molecular diagnosis. Methods Suspected CMS patients were divided into three groups: group A (limb, bulbar or axial weakness, with or without ocular impairment, and all the following: clinical fatigability, electrophysiology compatible with neuromuscular junction involvement and anticholinesterase agents response), group B (limb, bulbar or axial weakness, with or without ocular impairment, and at least one of additional characteristics noted in group A) and group C (pure ocular syndrome). Individual clinical findings and the clinical groups were compared between the group with a confirmed molecular diagnosis of CMS and the group without molecular diagnosis or with a non-CMS molecular diagnosis. Results Seventy-nine patients (68 families) were included in the cohort: 48 in group A, 23 in group B and 8 in group C. Fifty-one were considered confirmed CMS (30 CHRNE, 5 RAPSN, 4 COL13A1, 3 DOK7, 3 COLQ, 2 GFPT1, 1 CHAT, 1 SCN4A, 1 GMPPB, 1 CHRNA1), 7 probable CMS, 5 non-CMS and 16 unsolved. The chance of a confirmed molecular diagnosis of CMS was significantly higher for group A and lower for group C. Some individual clinical features, alterations on biopsy and electrophysiology enhanced specificity for CMS. Muscle imaging showed at least mild alterations in the majority of confirmed cases, with preferential involvement of soleus, especially in CHRNE CMS. Conclusions Stricter clinical criteria increase the chance of confirming a CMS diagnosis, but may lose sensitivity, especially for some specific genes.
- Facial and bulbar muscle atrophy in acetylcholine receptor antibody-positive myasthenia gravis(2017) GRATIVVOL, Ronnyson Susano; SILVA, Andre Macedo Serafim da; GUEDES, Brino Fukelmann; ESTEPHAN, Eduardo de Paula; MENDONCA, Rodrigo de Holanda; ZAMBON, Antonio Alberto; HEISE, Carlos Otto; ZANOTELI, Edmar