103 results on '"Lorenzoni PJ"'
Search Results
2. Rare but Relevant Kidney Disorders
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Glaudemans, B, primary, van der Wijst, J, additional, Scola, R, additional, Lorenzoni, PJ, additional, Heister, A, additional, van der Kemp, A, additional, Knoers, NV, additional, Hoenderop, JG, additional, and Bindels, RJ, additional
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- 2009
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3. Clinical and molecular characterization of limb-girdle muscular dystrophy 2G/R7 in a large cohort of Brazilian patients.
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Gaviraghi T, Cavalcanti EBU, Lorenzoni PJ, Cotta A, de Souza PVS, de Oliveira AD, de Moraes MT, Marques MVO, Donis KC, Winckler PB, Costa E Silva C, Pinto WBVR, Kay CSK, Ducci RD, Rodrigues PRVP, Fustes OJH, da Silva AMS, Zanoteli E, França MC Jr, Sobreira CFR, Oliveira ASB, Carvalho EHT, Scola RH, Carvalho AAS, and Saute JAM
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- Humans, Male, Brazil epidemiology, Female, Adult, Adolescent, Middle Aged, Child, Cohort Studies, Young Adult, Pedigree, Connectin genetics, Phenotype, Genetic Predisposition to Disease, Child, Preschool, Muscular Dystrophies, Limb-Girdle genetics, Muscular Dystrophies, Limb-Girdle epidemiology, Muscular Dystrophies, Limb-Girdle diagnosis, Mutation
- Abstract
Limb-girdle muscular dystrophy type 2G/R7 (LGMD2G/R7) is an ultra-rare condition initially identified within the Brazilian population. We aimed to expand clinical and genetic information about this disease, including its worldwide distribution. A multicenter historical cohort study was performed at 13 centers in Brazil in which data from index cases and their affected relatives from consecutive families with LGMD2G/R7 were reviewed from July 2017 to August 2023. Additionally, a systematic literature review was conducted to identify case reports and series of the disease worldwide. Forty-one LGMD2G/R7 cases were described in the Brazilian cohort, being all subjects homozygous for the c.157C>T/(p.Gln53*) variant in TCAP. Survival curves showed that the median disease duration before individuals required walking aids was 21 years. Notably, women exhibited a slower disease progression, requiring walking aids 13 years later than men. LGMD2G/R7 was frequently reported not only in Brazil but also in China and Bulgaria, with 119 cases identified globally, with possible founder effects in the Brazilian, Eastern European, and Asian populations. These findings are pivotal in raising awareness of LGMD2G/R7, understanding its progression, and identifying potential modifiers. This can significantly contribute to the development of future natural history studies and clinical trials for this disease., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2024
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4. Myopathy due to carnitine palmitoyltransferase II deficiency: updating genetic aspects of the first publication in Brazil.
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Lorenzoni PJ, Kay CSK, Ducci RD, Fustes OJH, Rodrigues PRDVP, Arndt RC, Scola RH, and Werneck LC
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- Humans, Carnitine O-Palmitoyltransferase genetics, Carnitine O-Palmitoyltransferase metabolism, Brazil, Mutation, Carnitine O-Palmitoyltransferase deficiency, Muscular Diseases genetics, Muscular Diseases pathology, Metabolism, Inborn Errors genetics, Metabolism, Inborn Errors metabolism, Metabolism, Inborn Errors pathology
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Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive inherited disorder related to lipid metabolism affecting skeletal muscle. The first cases of CPT II deficiency causing myopathy were reported in 1973. In 1983, Werneck et al published the first two Brazilian patients with myopathy due to CPT II deficiency, where the biochemical analysis confirmed deficient CPT activity in the muscle of both cases. Over the past 40 years since the pioneering publication, clinical phenotypes and genetic loci in the CPT2 gene have been described, and pathogenic mechanisms have been better elucidated. Genetic analysis of one of the original cases disclosed compound heterozygous pathogenic variants (p.Ser113Leu/p.Pro50His) in the CPT2 gene. Our report highlights the historical aspects of the first Brazilian publication of the myopathic form of CPT II deficiency and updates the genetic background of this pioneering publication., Competing Interests: There is no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)
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- 2024
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5. Clinical and genetic characterisation of a large Indian congenital myasthenic syndrome cohort.
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Polavarapu K, Sunitha B, Töpf A, Preethish-Kumar V, Thompson R, Vengalil S, Nashi S, Bardhan M, Sanka SB, Huddar A, Unnikrishnan G, Arunachal G, Girija MS, Porter A, Azuma Y, Lorenzoni PJ, Baskar D, Anjanappa RM, Keertipriya M, Padmanabh H, Harikrishna GV, Laurie S, Matalonga L, Horvath R, Nalini A, and Lochmüller H
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- Male, Female, Humans, Child, Adolescent, Young Adult, Adult, Acetylcholinesterase, Delayed Diagnosis, Neuromuscular Junction genetics, Genetic Testing, Mutation genetics, Myasthenic Syndromes, Congenital diagnosis
- Abstract
Congenital myasthenic syndromes (CMS) are a rare group of inherited disorders caused by gene defects associated with the neuromuscular junction and potentially treatable with commonly available medications such as acetylcholinesterase inhibitors and β2 adrenergic receptor agonists. In this study, we identified and genetically characterized the largest cohort of CMS patients from India to date. Genetic testing of clinically suspected patients evaluated in a South Indian hospital during the period 2014-19 was carried out by standard diagnostic gene panel testing or using a two-step method that included hotspot screening followed by whole-exome sequencing. In total, 156 genetically diagnosed patients (141 families) were characterized and the mutational spectrum and genotype-phenotype correlation described. Overall, 87 males and 69 females were evaluated, with the age of onset ranging from congenital to fourth decade (mean 6.6 ± 9.8 years). The mean age at diagnosis was 19 ± 12.8 (1-56 years), with a mean diagnostic delay of 12.5 ± 9.9 (0-49 years). Disease-causing variants in 17 CMS-associated genes were identified in 132 families (93.6%), while in nine families (6.4%), variants in genes not associated with CMS were found. Overall, postsynaptic defects were most common (62.4%), followed by glycosylation defects (21.3%), synaptic basal lamina genes (4.3%) and presynaptic defects (2.8%). Other genes found to cause neuromuscular junction defects (DES, TEFM) in our cohort accounted for 2.8%. Among the individual CMS genes, the most commonly affected gene was CHRNE (39.4%), followed by DOK7 (14.4%), DPAGT1 (9.8%), GFPT1 (7.6%), MUSK (6.1%), GMPPB (5.3%) and COLQ (4.5%). We identified 22 recurrent variants in this study, out of which eight were found to be geographically specific to the Indian subcontinent. Apart from the known common CHRNE variants p.E443Kfs*64 (11.4%) and DOK7 p.A378Sfs*30 (9.3%), we identified seven novel recurrent variants specific to this cohort, including DPAGT1 p.T380I and DES c.1023+5G>A, for which founder haplotypes are suspected. This study highlights the geographic differences in the frequencies of various causative CMS genes and underlines the increasing significance of glycosylation genes (DPAGT1, GFPT1 and GMPPB) as a cause of neuromuscular junction defects. Myopathy and muscular dystrophy genes such as GMPPB and DES, presenting as gradually progressive limb girdle CMS, expand the phenotypic spectrum. The novel genes MACF1 and TEFM identified in this cohort add to the expanding list of genes with new mechanisms causing neuromuscular junction defects., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2024
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6. Triple-seronegative myasthenia gravis: clinical and epidemiological characteristics.
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Rodrigues PRDVP, Kay CSK, Ducci RD, Utiumi MAT, Fustes OJH, Werneck LC, Lorenzoni PJ, and Scola RH
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- Female, Humans, Young Adult, Adult, Middle Aged, Retrospective Studies, Cross-Sectional Studies, Autoantibodies, Receptor Protein-Tyrosine Kinases, LDL-Receptor Related Proteins, Diplopia, Myasthenia Gravis diagnosis, Myasthenia Gravis drug therapy, Myasthenia Gravis epidemiology
- Abstract
Background: Myasthenia gravis (MG) is an autoimmune disease usually caused by antibodies against the acetylcholine receptor (AChR-Abs), muscle-specific tyrosine kinase (MuSK-Abs), or low-density lipoprotein receptor-related protein 4 (LRP4-Abs). However, there are MG patients who do not have these antibodies and are thus said to have triple-seronegative (triple-SN) MG., Objective: This study aims to describe the frequency and clinical and epidemiological characteristics of patients with triple-SN MG., Methods: This was a retrospective cross-sectional study carried out through the analysis of medical records. Descriptive and analytical statistical analysis was performed comparing subgroups of myasthenic patients, classified according to serological profile., Results: The sample population consisted of 93 MG patients: 85 were positive for antibodies, 80 (86%) with AChR-Abs, 5 (5.4%) with MuSK-Abs, and no MG patients with LRP4-Abs. Eight patients (8.6%) had triple-SN MG; they had a median age at disease onset of 30 years (21-45). Their most common initial symptoms were ptosis, diplopia, and generalized weakness. Most patients presented with mild symptoms at their last visit, reflecting a median MG composite scale score of 4 (0-6), and 75% of patients had an adequate response to treatment., Conclusion: Our study showed a low frequency of triple-SN MG in Brazilian MG patients. Triple-SN MG was predominant in females, who presented with ptosis, diplopia, and generalized weakness, and most patients had an adequate response to immunosuppressive treatment. There was no significant difference between triple-SN MG and the other subgroups., Competing Interests: There is no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)
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- 2024
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7. Single-centre experience with autosomal recessive limb-girdle muscular dystrophy: case series and literature review.
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Lorenzoni PJ, Kay CSK, Ducci RD, Fustes OJH, Rodrigues PRDVP, Hrysay NMC, Arndt RC, Werneck LC, and Scola RH
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- Humans, Anoctamins genetics, Brazil, Muscle Weakness, Pentosyltransferases genetics, Muscular Dystrophies, Limb-Girdle genetics
- Abstract
Limb-girdle muscular dystrophy (LGMD) is a group of myopathies that lead to progressive muscle weakness, predominantly involving the shoulder and pelvic girdles; it has a heterogeneous genetic etiology, with variation in the prevalence of subtypes according to the ethnic backgrounds and geographic origins of the populations. The aim of the present study was to analyze a series of patients with autosomal recessive LGMD (LGMD-R) to contribute to a better characterization of the disease and to find the relative proportion of the different subtypes in a Southern Brazil cohort. The sample population consisted of 36 patients with LGMD-R. A 9-gene targeted next-generation sequencing panel revealed variants in 23 patients with LGMD (64%), and it identified calpainopathy (LGMD-R1) in 26%, dysferlinopathy (LGMD-R2) in 26%, sarcoglycanopathies (LGMD-R3-R5) in 13%, telethoninopathy (LGMD-R7) in 18%, dystroglicanopathy (LGMD-R9) in 13%, and anoctaminopathy (LGMD-R12) in 4% of the patients. In these 23 patients with LGMD, there were 27 different disease-related variants in the ANO5 , CAPN3 , DYSF , FKRP , SGCA , SGCB , SGCG , and TCAP genes. There were different causal variants in different exons of these genes, except for the TCAP gene, for which all patients carried the p.Gln53* variant, and the FKRP gene, which showed recurrence of the p.Leu276Ile variant. We analyzed the phenotypic, genotypic and muscle immunohistochemical features of this Southern Brazilian cohort., Competing Interests: The authors have no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)
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- 2023
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8. Genetic screening for transthyretin familial amyloid polyneuropathy to avoid misdiagnosis in patients with polyneuropathy associated with high protein in the cerebrospinal fluid.
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Lorenzoni PJ, Giugno VR, Ducci RD, Werneck LC, Kay CSK, and Scola RH
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- Humans, Prealbumin genetics, Mutation, Genetic Testing, Diagnostic Errors, Amyloid genetics, Amyloid metabolism, Amyloid Neuropathies, Familial diagnosis, Amyloid Neuropathies, Familial genetics, Polyneuropathies diagnosis, Polyneuropathies genetics
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- 2023
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9. Spectrum of SPTLC1-related disorders: a novel case of 'Ser331 syndrome' that expand the phenotype of hereditary sensory and autonomic neuropathy type 1A and motor neuron diseases.
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Lorenzoni PJ, Bayer DL, Ducci RD, Fustes OJH, do Vale Pascoal Rodrigues PR, Werneck LC, Kay CSK, and Scola RH
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- Humans, Serine C-Palmitoyltransferase genetics, Fasciculation, Phenotype, Mutation genetics, Atrophy, Hereditary Sensory and Autonomic Neuropathies diagnosis, Hereditary Sensory and Autonomic Neuropathies genetics, Motor Neuron Disease complications, Motor Neuron Disease genetics
- Abstract
We report a patient with early-onset hereditary sensory and autonomic neuropathy type 1A (HSAN-1A) who developed a distinct phenotype, with tongue fasciculation and atrophy, due to a mutation at serine 331 in the SPTLC1 gene. HSAN-1A manifestation causing tongue fasciculation and atrophy have been rarely found. Our report adds to the growing evidence of the existence of an overlap between hereditary neuropathy and motor neuron disease caused by pathogenic p.S331Y variant in SPTLC1 gene., (© 2023. Fondazione Società Italiana di Neurologia.)
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- 2023
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10. Pain-related nociceptive evoked potential and skin wrinkle test in small fiber neuropathy.
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Hernández Fustes OJ, Kay CSK, Lorenzoni PJ, Ducci RD, Ribas MZ, Werneck LC, and Scola RH
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- Evoked Potentials, Humans, Nociception, Skin, Neuralgia diagnosis, Small Fiber Neuropathy diagnosis
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- 2022
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11. Peripheral polyneuropathy from electrodiagnostic tests: a 10-year etiology and neurophysiology overview.
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Ducci RD, Tessaro CL, Kay CSK, Fustes OJH, Werneck LC, Lorenzoni PJ, and Scola RH
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- Adult, Axons, Cross-Sectional Studies, Female, Humans, Male, Physical Examination, Electrodiagnosis adverse effects, Neurophysiology, Polyneuropathies diagnosis, Polyneuropathies etiology
- Abstract
Background: Polyneuropathies are characterized by a symmetrical impairment of the peripheral nervous system, resulting in sensory, motor and/or autonomic deficits. Due to the heterogeneity of causes, an etiological diagnosis for polyneuropathy is challenging., Objective: The aim of this study was to determine the main causes of polyneuropathy confirmed by electrodiagnostic (EDX) tests in a tertiary service and its neurophysiological aspects., Methods: This observational cross-sectional study from a neuromuscular disorders center included individuals whose electrodiagnostic tests performed between 2008 and 2017 confirmed a diagnosis of polyneuropathy. Through analysis of medical records, polyneuropathies were classified according to etiology and neurophysiological aspect., Results: Of the 380 included patients, 59.5% were male, with a median age of 43 years. The main etiologies were: inflammatory (23.7%), hereditary (18.9%), idiopathic (13.7%), multifactorial (11.1%), and diabetes (10.8%). The main electrophysiological patterns were axonal sensorimotor polyneuropathy (36.1%) and "demyelinating and axonal" sensorimotor polyneuropathy (27.9%). Axonal patterns showed greater etiological heterogeneity, with a predominance of idiopathic and multifactorial polyneuropathy, while demyelinating and "demyelinating and axonal" polyneuropathies had a significantly fewer etiologies, with a predominance of hereditary and inflammatory polyneuropathies., Conclusion: The main causes of polyneuropathy confirmed by EDX test in this study were those that presented a severe, atypical and/or rapidly progressing pattern. Other causes were hereditary and those that defy clinical reasoning, such as multiple risk factors; some polyneuropathies did not have a specific etiology. EDX tests are useful for etiological diagnosis of rare polyneuropathies, because neurophysiological patterns are correlated with specific etiologies.
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- 2022
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12. Seventy years since the invention of the averaging technique in Neurophysiology: Tribute to George Duncan Dawson.
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Fustes OJH, Kay CSK, Lorenzoni PJ, Ducci RD, Werneck LC, and Scola RH
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- Evoked Potentials, Evoked Potentials, Somatosensory, Evoked Potentials, Visual, History, 20th Century, Humans, Inventions, Neurophysiology methods
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Objective: In 1951, the physiologist George Duncan Dawson presented his work with the averaging of the signal in the evoked potentials (EPs), opening a new stage in the development of clinical neurophysiology. The authors present aspects of Professor Dawson's biography and a review of his work on the EPs and, mainly, the article reveals the new technique in detail that would allow the growth of the clinical application of the visual, auditory, and somatosensory EPs.
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- 2022
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13. Congenital myasthenic syndrome in a cohort of patients with 'double' seronegative myasthenia gravis.
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Lorenzoni PJ, Ducci RD, Arndt RC, Hrysay NMC, Fustes OJH, Töpf A, Lochmüller H, Werneck LC, Kay CSK, and Scola RH
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- Cohort Studies, Genetic Testing, Humans, Mutation, Myasthenia Gravis diagnosis, Myasthenia Gravis genetics, Myasthenic Syndromes, Congenital diagnosis, Myasthenic Syndromes, Congenital genetics
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Background: Congenital myasthenic syndromes (CMS) have some phenotypic overlap with seronegative myasthenia gravis (SNMG)., Objective: The aim of this single center study was to assess the minimum occurrence of CMS misdiagnosed as double SNMG in a Brazilian cohort., Methods: The genetic analysis of the most common mutations in CHRNE, RAPSN, and DOK7 genes was used as the main screening tool., Results: We performed genetic analysis in 22 patients with a previous diagnosis of 'double' SNMG. In this study, one CMS patient was confirmed due to the presence of compound heterozygous variants in the CHRNE gene (c.130insG/p.Cys210Phe)., Conclusions: This study confirmed that CMS due to CHNRE mutations can be mistaken for SNMG. In addition, our study estimated the prevalence of misdiagnosed CMS to be 4.5% in 'double' SNMG patients of our center. Based on our findings, genetic screening could be helpful in the diagnostic workup of patients with 'double' SNMG in whom differential diagnosis is recommended.
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- 2022
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14. Charcot-Marie-Tooth disease type 4C associated with myasthenia gravis: coincidental or a foreseeable association?
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Lorenzoni PJ, Kay CSK, Ducci RD, Fustes OJH, Werneck LC, and Scola RH
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- Humans, Neuromuscular Junction, Charcot-Marie-Tooth Disease complications, Myasthenia Gravis complications
- Abstract
We reported one patient with Charcot-Marie-Tooth type 4C (CMT4C) who developed seropositive myasthenia gravis. Neuromuscular junction alterations in CMT4C patients have not yet been reported. However, few patients have been reported to simultaneously have MG and CMT, but none with CMT4C. Our report suggests that additional research is required to confirm whether genetic neuropathies may predispose to MG., (© 2021. Fondazione Società Italiana di Neurologia.)
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- 2022
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15. Visual Evoked Potentials in Neuromyelitis Optica Spectrum Disorders.
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Hernandez Fustes OJ, Kay CSK, Lorenzoni PJ, Ducci RD, Werneck LC, and Scola RH
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Background: Neuromyelitis optica spectrum disorders (NMOSDs) are rare antibody-mediated disorders of the central nervous system, with a predilection for the spinal cord and optic nerves. The clinical utility of evoked potential recordings (EPs) has already been established for multiple sclerosis, in particular, that of the abnormal visual evoked potentials (VEP), a key criterion in the McDonald diagnostic criteria for MS. However, there have been few reports on EPs in patients with NMOSD., Aim: The aim of our study was to assess the possible involvement of the optical pathway through VEP responses in patients with NMOSD., Methods: VEPs were prospectively performed in 13 patients with NMOSD. All the patients were recruited from the outpatient clinic of a demyelinating diseases center. The recording was done as recommended by the International Federation of Clinical Neurophysiology., Results: We evaluated the eyes of 12 women with a mean age of 42 years and of one man who was 25 years old. In 6 of the examined eye samples, a response was not obtained, while in the remaining 20 eye samples, we found a significant increase in P100 latency without amplitude change., Conclusion: VEPs showed a significant increase in P100 latency. VEP assessment is a non-invasive, painless, fast, and low-cost exam that provides neurophysiological data for diagnosis of NMOSD., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)
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- 2021
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16. Somatosensory evoked potentials in clinical practice: a review.
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Fustes OJH, Kay CSK, Lorenzoni PJ, Ducci RD, Werneck LC, and Scola RH
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- Humans, Evoked Potentials, Motor, Evoked Potentials, Somatosensory
- Abstract
The authors present a review of the current use of somatosensory evoked potentials (SSEPs) in neurological practice as a non-invasive neurophysiological technique. For this purpose we have reviewed articles published in English or Portuguese in the PubMed and LILACS databases. In this review, we address the role of SSEPs in neurological diseases that affect the central nervous system and the peripheral nervous system, especially in demyelinating diseases, for monitoring coma, trauma and the functioning of sensory pathways during surgical procedures. The latter, along with new areas of research, has become one of the most important applications of SSEPs.
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- 2021
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17. Myasthenia gravis during pregnancy: what care should be taken?
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Ducci RD, Kay CSK, Fustes OJH, Werneck LC, Lorenzoni PJ, and Scola RH
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- Child, Female, Humans, Infant, Newborn, Postpartum Period, Pregnancy, Myasthenia Gravis drug therapy, Pregnancy Complications therapy
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Myasthenia gravis (MG) is an autoimmune disease in which the peak incidence is among women of childbearing age. For this reason, there is an overlap between the occurrence of this disease and pregnancy. It is known that MG symptoms can worsen during pregnancy and postpartum, and that pregnancy has special characteristics in MG patients. Children born to myasthenic mothers are at risk of having transient neonatal myasthenia. We briefly review the main relationships between MG and pregnancy, and we make recommendations for MG therapy, pregnancy, delivery, breastfeeding and newborns.
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- 2021
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18. Horner syndrome: tribute to Professor Horner on his 190th birthday.
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Fustes OJH, Kay CSK, Lorenzoni PJ, Ducci RD, Werneck LC, and Scola RH
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- History, 19th Century, Humans, Neck, Blepharoptosis, Horner Syndrome
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This paper reviews some aspects of the life and work of Professor Johann Friedrich Horner, on the occasion of the 190th anniversary of his birthday and 152 years after the publication of "Über eine Form von Ptosis". It also shows the importance of the historical description of ptosis, myosis and anhidrosis associating those symptoms with sympathetic cervical damage. He pharmacologically confirmed the impairment of sympathetic innervation to the eye and preserved parasympathetic function.
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- 2021
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19. "On the Ophthalmoscopic Signs of Spinal Disease" 150 Years Later: A Tribute to Professor Sir Thomas Clifford Allbutt.
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Hernandez Fustes OJ, Kamoi Kay CS, Lorenzoni PJ, Dal-Prá Ducci R, Werneck LC, and Scola RH
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- England, History, 19th Century, History, 20th Century, Humans, Neuromyelitis Optica diagnosis, Spinal Diseases diagnosis, Neuromyelitis Optica history, Ophthalmology history, Ophthalmoscopes history, Spinal Diseases history
- Abstract
Competing Interests: The authors report no conflicts of interest.
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- 2021
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20. Denny-Brown and Pennybacker: 80 years after their pioneering article on electromyography, fibrillation and fasciculation.
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Hernandez Fustes OJ, Kay CSK, Lorenzoni PJ, Ducci RD, Werneck LC, and Scola RH
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- Arrhythmias, Cardiac, Fasciculation diagnosis, History, 20th Century, History, 21st Century, Humans, Amyotrophic Lateral Sclerosis diagnosis, Electromyography history, Physicians
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We present a historical review, highlighting the role of Professor Derek Denny-Brown and doctor Joseph Buford Pennybacker in the development of current electromyography (EMG), of the 80 years since the publication of his original report in 1938 on fasciculation and fibrillation potentials and the subsequent studies describing most of the electrical changes necessary to perform and interpret the EMG.
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- 2021
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21. Somatosensory evoked potentials in Hirayama disease: A Brazilian study.
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Fustes OH, Kay CSK, Lorenzoni PJ, Ducci RD, Werneck LC, and Scola RH
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Background: Hirayama's disease (HD) is characterized by an insidious onset asymmetric weakness and atrophy of the forearm and hand. Taking as a premise, the etiopathogenesis of the disease is attributed to forward displacement of posterior wall of lower cervical dural canal in neck flexion causing marked compression and flattening of lower spinal cord. This may result in compression of the posterior column of the spinal cord and seems likely to result in somatosensory evoked potentials (SSEPs) abnormalities. In the present study, we studied the possible involvement of the lemniscal dorsal pathway in patients with HD., Methods: SSEPs in upper and lower extremities were prospectively performed in eight patients with HD. All the patients were recruited from the outpatient clinic of a neuromuscular disorder center from South Brazil. SSEPs were obtained by transcutaneous electrical stimulation of the median and posterior tibial nerves, on both sides. We collected the amplitude and the latency of the different components obtained in each channel. The interpretation was based on Brazilian study standards., Results: We evaluated seven men and one woman (mean age 27). The data obtained were compared to a control group consisting of eight patients with spondylotic cervical myelopathy, 6 men and 2 women with mean age of 59 years. The measurements of obtained by the SSEP were also compared between the groups and no significant difference was found for any of them., Conclusion: SSEP did not turn out to be an electrophysiological marker in our HD patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Surgical Neurology International.)
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- 2020
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22. Does oral salbutamol improve fatigue in multiple sclerosis? A pilot placebo-controlled study.
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de Almeida GM, Scola RH, Ducci RDP, Cirino RHD, Cláudia SKK, Lorenzoni PJ, Lima PHS, de Oliveira LP, and Werneck LC
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- Adolescent, Adult, Aged, Albuterol therapeutic use, Brazil, Double-Blind Method, Fatigue drug therapy, Fatigue etiology, Humans, Middle Aged, Multiple Sclerosis, Relapsing-Remitting complications, Multiple Sclerosis, Relapsing-Remitting drug therapy, Young Adult, Multiple Sclerosis complications, Multiple Sclerosis drug therapy
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Background: Because MS-related fatigue could be associated with enhanced proinflammatory cytokine production, drugs with immunomodulatories properties, such as salbutamol, may represent an alternative treatment. We aimed to evaluate the effect of salbutamol on MS-related fatigue., Methods: Thirty patients with relapsing-remitting MS who were between 18 and 69 years old, and suffering from fatigue, were evaluated with the Fatigue Severity Scale (FSS) and the Brazilian version of the neurological fatigue index for multiple sclerosis (NFI/MS-BR). They received salbutamol 2 mg twice a day or a placebo in a pilot randomized, double-masked placebo-controlled trial. The primary outcome was the change in the FSS score at the end of 90 days. The secondary outcome was the efficacy, represented by changes in their scores on the NFI/MS-BR subdomains (in the same period) and the Expanded Disability Status Scale (EDSS) at the end of 90 days., Results: Thirty subjects were allocated to receive either salbutamol (14) or a placebo (16). There was no superiority of salbutamol over the placebo in the FSS outcome at 30 (p ==0.498), 60 (p = 0.854) and 90 (p = 0.240) days. There was no a significant decrease in the proportion of patients with severe or moderate fatigue in the salbutamol group at the end of the follow-up. The scores on the NFI/MS-BR and its subscales did not improve significantly with treatment. No significant difference was observed in the EDSS outcome (p = 0.313). No serious adverse events were found. An increase in heart rate was evident in the salbutamol group only in the first 30 days, but without statistical significance in relation to placebo (p = 0.077)., Conclusion: Treatment with salbutamol does not improve fatigue in patients with relapsing-remitting MS., (Copyright © 2020 Elsevier B.V. All rights reserved.)
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- 2020
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23. Localized sporotrichosis during natalizumab treatment in Multiple Sclerosis.
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Marques PT, Kay CSK, Basílio FMA, Pinheiro RL, Werneck LC, Lorenzoni PJ, and Scola RH
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- Humans, Immunologic Factors adverse effects, Male, Middle Aged, Natalizumab adverse effects, Immunologic Factors therapeutic use, Multiple Sclerosis drug therapy, Multiple Sclerosis microbiology, Natalizumab therapeutic use, Sporotrichosis etiology
- Abstract
Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare.
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- 2020
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24. Myasthenia gravis and azathioprine treatment: Adverse events related to thiopurine S-methyl-transferase (TPMT) polymorphisms.
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Lorenzoni PJ, Kay CSK, Zanlorenzi MF, Ducci RD, Werneck LC, and Scola RH
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- Brazil, Genotype, Humans, Methyltransferases genetics, Transferases, Azathioprine adverse effects, Myasthenia Gravis genetics
- Abstract
Azathioprine (AZA) is the most common immunosuppressive drug used to treat myasthenia gravis (MG). To analyses the prevalence of thiopurine S-methyl-transferase (TPMT) genotypes and their association with adverse events due to azathioprine therapy in MG patients. Allele-specific polymerase chain reaction (PCR) and PCR with restriction fragment length polymorphism (RFLP) analysis were carried out to determine the prevalence of the most common TPMT genotypes (*2, *3A, *3B and *3C) in 50 MG patients from Southern Brazilian. The frequency of adverse reactions due to azathioprine therapy was analysed and correlated with different genotypes groups. The prevalence of TPMT gene variants was 12%. The allelic frequency of variant TPMT*2 (C238G), TPMT*3A (G460A/A719G), TPMT*3B (G460A), and TPMT*3C (A719G) genotypes was 1, 3, 2 and 1%, respectively. Adverse events occurred in 44%, of MG patients, of which 86% were minor and 14% were major. One patient, who presented a major adverse event (bone marrow suppression), was homozygous for the TPMT*3A genotype. Our study estimated the prevalence of TPMT genotypes for Brazilian MG patients. The profile of TPMT genotypes was different from other Brazilian populations. Hardy-Weinberg equilibrium and allelic frequencies of TPMT*3A and TPMT*3B, respectively, were different than expected, a finding that suggests a possible founder effect. Major adverse events were statistically significant for TPMT genotypes compared to wild-type. Although TPMT genotype has been associated with AZA-related adverse events, since no statistically significant difference among wild-type and other TPMT genotypes for minor adverse events, our study supports the view that TPMT genotype alone is not enough to adequately personalise the AZA therapy in MG patients. In conclusion, these results were important to characterise the prevalence of TPMT gene variants in MG patients treated with AZA and correlate the adverse events of this therapy in a real-world outpatient clinic from Southern Brazil., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)
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- 2020
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25. Characterization of the amyotrophic lateral sclerosis-linked P56S mutation of the VAPB gene in Southern Brazil.
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Trilico MLC, Lorenzoni PJ, Kay CSK, Ducci RDP, Fustes OJH, Werneck LC, and Scola RH
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- Adult, Aged, Amyotrophic Lateral Sclerosis epidemiology, Brazil epidemiology, Cohort Studies, Female, Humans, Male, Middle Aged, Retrospective Studies, Amyotrophic Lateral Sclerosis diagnosis, Amyotrophic Lateral Sclerosis genetics, Mutation genetics, Vesicular Transport Proteins genetics
- Abstract
Objective : Amyotrophic lateral sclerosis (ALS) is a rare worldwide heterogeneous neurodegenerative disease with sporadic and familial (FALS) forms. A rare autosomal dominant subtype of FALS was identified in a Brazilian family, classified as ALS type 8 (ALS8) linked to the VAPB gene. The aim of our study was to analyze a series of ALS8 patients from unrelated families in order to further characterize the disease. Methods: We reviewed only patients with probable or definite ALS according to the Awaji criteria being managed at a single center between 2004 and 2018 and with DNA samples available for genetic analysis. A retrospective analysis of clinical, laboratory, and electrophysiological features was performed, relevant data were recorded and DNA was analyzed to detect VAPB gene mutation. Results: Thirty-one ALS patients were eligible for genetic screening for ALS8 and the mutation was detected in five patients from unrelated families. The mean age of onset was 45 ± 5.3 years for the ALS8 group and 47.6 ± 13.1 years for the non-ALS8 group and the time between symptom onset and last follow-up was longer for ALS8 patients. Three patients in the ALS8 group had tremor (60%), four had pain in affected limb (80%) and all had cramps and abdominal protrusion. Conclusions: This study presents the largest series of ALS8 patients in southern Brazil. Our findings demonstrate several clinical features that may be characteristic of ALS8 and confirm that clinicians should suspect ALS8 when the clinical manifestations include cramps, abdominal protrusion, pain, and tremor.
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- 2020
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26. Reply.
- Author
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Werneck LC, Lorenzoni PJ, Ducci RD, Fustes OH, Kay CSK, and Scola RH
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- Humans, Muscular Dystrophy, Duchenne
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- 2020
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27. Congenital myasthenic syndrome due to DOK7 mutation in a cohort of patients with 'unexplained' limb-girdle muscular weakness.
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Lorenzoni PJ, Kay CSK, Arndt RC, Hrysay NMC, Ducci RD, Fustes OHJ, Töpf A, Lochmüller H, Werneck LC, and Scola RH
- Subjects
- Adolescent, Adult, Aged, Brazil epidemiology, Cohort Studies, Female, Genetic Testing methods, Humans, Male, Middle Aged, Muscle Weakness diagnosis, Muscle Weakness epidemiology, Muscle Weakness genetics, Muscular Dystrophies, Limb-Girdle epidemiology, Myasthenic Syndromes, Congenital epidemiology, Retrospective Studies, Young Adult, Muscle Proteins genetics, Muscular Dystrophies, Limb-Girdle diagnosis, Muscular Dystrophies, Limb-Girdle genetics, Mutation genetics, Myasthenic Syndromes, Congenital diagnosis, Myasthenic Syndromes, Congenital genetics
- Abstract
Congenital myasthenic syndromes (CMS) associated with pathogenic variants in the DOK7 gene (DOK7-CMS) have phenotypic overlap with other neuromuscular disorders associated with limb-girdle muscular weakness (LGMW). Genetic analysis of the most common mutation (c.1124_1127dupTGCC) in DOK7 was performed in 34 patients with "unexplained" LGMW associated with non-specific changes in muscle biopsy. Of the 34 patients, one patient showed the DOK7 c.1124_1127dupTGCC variant in homozygousity. Our study estimates the minimum prevalence of undiagnosed DOK7-CMS to be 2.9% in southern Brazilian patients from our centre. Our data confirm that clinicians should look for DOK7-CMS patients when the clinical manifestation is an 'unexplained' LGMW, mainly if associated with non-specific changes in muscle biopsy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)
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- 2020
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28. Single-centre experience on genotypic and phenotypic features of southern Brazilian patients with McArdle disease.
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Lorenzoni PJ, Werneck LC, Kay CSK, Arndt RC, Silvado CES, and Scola RH
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- Adolescent, Adult, Brazil, Female, Genotype, Glycogen Phosphorylase, Muscle Form genetics, Glycogen Storage Disease Type V genetics, Humans, Male, Middle Aged, Mutation, Phenotype, Young Adult, Glycogen Storage Disease Type V pathology, Glycogen Storage Disease Type V physiopathology
- Abstract
McArdle disease (MD) is a metabolic myopathy caused by deficiency of the myophosphorylase enzyme. The aim of our study was to analyse a series of MD patients in Brazil and the correlation between clinical findings, laboratory data, electromyography, muscle biopsy and genetic features. The PYGM gene was analysed by PCR/RLFP and Sanger sequencing. The sample included 12 patients, aged 18-57 years, from unrelated families. Exercise intolerance was present in all cases. Serum creatine kinase levels at rest were increased in all patients. Forearm ischaemic exercise testing in five patients revealed no increase in venous lactate. Needle electromyography presented 'myopathic pattern' in six patients. Muscle biopsy showed vacuolar myopathy in 10 patients and deficiency of myophosphorylase enzyme in all patients. The genetic analysis showed p.R50X as the most common mutation (allelic frequency: 56.25%), other known mutations (p.Y574X, p.G205S, p.W798R, IVS14 + 1G > A and IVS19-1G > A) and a new mutation (p.Asn168Lysfs*15) were also identified. Several features of the disorder were similar to the vast majority of patients worldwide. The genetic findings of this study revealed a range of mutations that are quite similar to the European cohort. The discovery of one novel mutation increases the genotypic heterogeneity of PYGM gene.
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- 2020
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29. Celebrating the 70 years of pyridostigmine on therapy of Myasthenia Gravis: historical aspects of the preliminary trials.
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Lorenzoni PJ, Kay CSK, Ducci RD, Fustes OJH, Werneck LC, and Scola RH
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- Humans, Cholinesterase Inhibitors therapeutic use, Myasthenia Gravis drug therapy, Pyridostigmine Bromide therapeutic use
- Abstract
Currently, pyridostigmine bromide is an indispensable anticholinesterase agent used worldwide to treat patients with Myasthenia Gravis (MG). However, pyridostigmine bromide was unsuccessful in its "pioneering trials" to treat a series of MG patients. There are important historical landmarks before pyridostigmine bromide becomes useful, safe and indispensable for MG therapy. After 70 years of these "pioneering trials", this article reviews some historical aspects related to them, as well as other preliminary trials using pyridostigmine bromide as therapy for MG patients.
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- 2020
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30. 140 Years of the Leçons sur l'histologie du système nerveux: the pioneering description of the nodes of Ranvier.
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Hernandez Fustes OJ, Kay CSK, Lorenzoni PJ, Ducci RD, Barbara JG, Werneck LC, and Scola RH
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- History, 19th Century, History, 20th Century, Nerve Fibers, Myelinated, Paris, Nervous System anatomy & histology, Neurology history, Ranvier's Nodes
- Abstract
This paper reviews aspects of the life and work of Professor Louis Ranvier 140 years after the publication of Leçons sur l'histologie du système nerveux, published in 1878, and shows the importance of the histological description of myelinated fibers of the nodes of Ranvier.
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- 2019
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31. Duchenne muscular dystrophy: an historical treatment review.
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Werneck LC, Lorenzoni PJ, Ducci RD, Fustes OH, Kay CSK, and Scola RH
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- Adrenal Cortex Hormones therapeutic use, Anti-Inflammatory Agents therapeutic use, Antioxidants therapeutic use, Calcium Channel Blockers therapeutic use, Cholinesterase Inhibitors therapeutic use, Dystrophin drug effects, Dystrophin metabolism, Humans, Muscular Dystrophy, Duchenne metabolism, Muscular Dystrophy, Duchenne drug therapy
- Abstract
In this review, we discuss the therapies used in the treatment of patients with Duchenne muscular dystrophy since the first description of the disease. A short description is given of the various theories based on disease pathogenesis, which give the substrates for the many therapeutic interventions. A brief review of the methods of evaluation used in therapeutic trials is made. Of all the treatments, the only drugs that are still considered able to modify the course of the disease are the corticosteroids (prednisone/prednisolone/deflazacort). Other drugs (coenzyme Q10 and creatine) have had a little effect in a few functions without adverse reactions. Idebenone seems to improve the respiratory function in the long term. The trials with mRNA transcription, through nonsense mutations or exon 51 skipping, show some beneficial results in a few functional tests, but they are limited to a small set of DMD patients.
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- 2019
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32. Diaphragm quantitative electromyography: upgrading an important tool in the search for diaphragmatic myopathy in asthmatic patients.
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Lorenzoni PJ
- Subjects
- Diaphragm, Electromyography, Humans, Asthma, Muscular Diseases
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- 2019
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33. HLA-alleles class I and II associated with genetic susceptibility to neuromyelitis optica in Brazilian patients.
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Kay CSK, Scola RH, Arndt RC, Lorenzoni PJ, and Werneck LC
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- Adult, Brazil, Case-Control Studies, Female, Gene Frequency, Genotype, Humans, Male, Middle Aged, Polymerase Chain Reaction, Reference Values, Young Adult, Alleles, Genes, MHC Class I genetics, Genes, MHC Class II genetics, Genetic Predisposition to Disease genetics, HLA Antigens genetics, Neuromyelitis Optica genetics
- Abstract
Objective: To study the genetic susceptibility to neuromyelitis optica (NMO) as well as the relationship between HLA genotypes and susceptibility to the disease in the southern Brazilian population., Methods: We analyzed patients with NMO, who met criteria for Wingerchuk's diagnosis of NMO, with detected serum anti-AQP4-IgG antibody. The HLA genotyping was performed by high-resolution techniques (Sanger sequencing) in patients and controls. The HLA genotypes were statistically compared with a paired control population., Results: The HLA genotyping revealed the diversity of the southern Brazilian population whose HLA profile resembled European and Asian populations. Some alleles had statistical correlations with a positive association (increased susceptibility) with NMO, particularly the HLA-DRB1*04:05 and *16:02., Conclusions: In our study, the HLA genotype was different to that previously reported for other Brazilian populations. Although our study had a small cohort, HLA genotypes were associated with increased susceptibility to NMO for HLA-DRB1*04:05 and *16:02. The alleles of HLA class I HLA-A*02:08 and *30:09, HLA-B*08:04 and *35:04 showed an association before the Bonferroni correction.
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- 2019
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34. Evaluation of Left-Sided Heart Chambers With Novel Echocardiographic Techniques in Men With Duchenne or Becker Muscular Dystrophy.
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Cirino RHD, Scola RH, Ducci RD, Camarozano AC, Kay CSK, Lorenzoni PJ, Werneck LC, Carmes ER, and da Cunha CLP
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- Adolescent, Child, Heart Atria physiopathology, Heart Ventricles physiopathology, Humans, Male, Reproducibility of Results, Retrospective Studies, Systole, Ventricular Dysfunction, Left etiology, Ventricular Dysfunction, Left physiopathology, Atrial Function, Left physiology, Echocardiography, Three-Dimensional methods, Heart Atria diagnostic imaging, Heart Ventricles diagnostic imaging, Muscular Dystrophy, Duchenne complications, Ventricular Dysfunction, Left diagnosis, Ventricular Function, Left physiology
- Abstract
Left ventricular systolic dysfunction (LVSD) is a common finding in patients with Duchenne (DMD) and Becker (BMD) muscular dystrophies. Novel echocardiographic techniques have been used for the detection of LVSD in several heart diseases. We aim to compare cardiac anatomic and functional data studied by three-dimensional (3DE) and two-dimensional (2DE) echocardiography and to analyze the myocardial strain for the detection of early LVSD in DMD and BMD patients. We performed a cross-sectional study of 46 DMD and 14 BMD patients. We measured left atrium volume and left ventricle volumes and ejection fraction using 3DE and 2DE techniques. Myocardial strain analysis was derived from global longitudinal strain (GLS) measurements. GLS was measured by 2DE with the speckle tracking technique. The correlation between 3DE and 2DE for the measurement of left atrium volume as well as left ventricle diastolic and systolic volumes was strong. 2DE presented larger left atrium and left ventricle volumes. Left ventricle ejection fraction was similar between the two techniques. Myocardial strain analysis was able to detect early LVSD in 50.0% of DMD patients and in 9.1% of BMD patients. In conclusion, two-dimensional echocardiography appears to be a good alternative for the anatomical and functional evaluation of the left heart chambers in DMD and BMD patients. Myocardial strain analysis detects early LVSD in a sizable portion of patients with dystrophinopathies., (Copyright © 2018 Elsevier Inc. All rights reserved.)
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- 2019
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35. Multiple sclerosis: disease modifying therapy and the human leukocyte antigen.
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Werneck LC, Lorenzoni PJ, Kay CSK, and Scola RH
- Subjects
- Adolescent, Adult, Alleles, Child, Disease Progression, Female, Gene Frequency genetics, Genetic Predisposition to Disease, Genotype, HLA-D Antigens genetics, Humans, Immunosuppressive Agents therapeutic use, Male, Middle Aged, Multiple Sclerosis, Relapsing-Remitting drug therapy, Severity of Illness Index, Time Factors, Treatment Outcome, Young Adult, HLA Antigens genetics, Multiple Sclerosis, Relapsing-Remitting genetics
- Abstract
Objective: To investigate the potential relationship between the human leukocyte antigen (HLA) type (class I and II) and the response to several disease-modifying therapies (DMTs) in patients with multiple sclerosis (MS)., Methods: We analyzed clinical data of 87 patients with MS at the beginning and end of each type of DMT including the disease duration, Expanded Disability Status Scale and Multiple Sclerosis Severity Score (MSSS). Genotyping of HLA-DRB1, HLA-DPB1, HLA-DQB1, HLA-A, HLA-B and HLA-C alleles were identified using high-resolution techniques. Statistical correlation between the HLA type and response to DMTs was done using the initial and final MSSS., Results: Statistical relationships (p < 0.05) were found for only 15 of 245 alleles tested. There was a reduction in the MSSS for patients treated with corticosteroids (DRB1*15:01, DPB1*04:01, DQB1*02:01 and DQB1*03:01), azathioprine (DRB1*03:01, DPB1*04:01, DQB1*03:02, DQB1*06:02, HLA-C*07:02), interferon β-1a 22 mcg (DRB1*11:04, DQB1*03:01 and DQB1*03:02), interferon β-1a 30 mcg (DPB1*02:01, HLA-C*05:01) and interferon β-1b (DQB1*02:01)., Conclusion: These findings suggest a few relationships between the HLA and response to DMTs in the disability for some types of HLA class I and II alleles in a specific subset of MS patients.
- Published
- 2018
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36. Motor neuron disease in patients with HIV infection: Report of two cases and brief review of the literature.
- Author
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Lorenzoni PJ, Ducci RD, Dalledone GO, Kay CSK, de Almeida SM, Werneck LC, and Scola RH
- Subjects
- Amyotrophic Lateral Sclerosis complications, Amyotrophic Lateral Sclerosis diagnosis, Brazil, Diagnosis, Differential, Female, Humans, Male, Middle Aged, Motor Neuron Disease complications, Motor Neuron Disease diagnosis, Amyotrophic Lateral Sclerosis virology, HIV pathogenicity, Motor Neuron Disease virology, Motor Neurons virology
- Abstract
HIV-associated motor neuron disease (MND), or amyotrophic lateral sclerosis (ALS)-like syndrome associated with HIV infection, is a rare manifestation of HIV infection. HIV-associated MND has only been identified in few cases to date. We analysed two Brazilian patients with HIV infection who developed MND. The diagnosis of HIV infection was concomitant with diagnosis of MND in one patient and it occurred eight years before the MND symptoms in another patient. The manifestation of MND in our patients with HIV infection was similar to classic ALS. The antiretroviral therapy improves their HIV infection. However, slow progression of MND occurred in the two patients despite their antiretroviral therapy or HIV viral load (undetectable). We revised the international literature (PubMed database) of the patients reported with MND and HIV infection., (Copyright © 2018. Published by Elsevier B.V.)
- Published
- 2018
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37. Recessive variants of MuSK are associated with late onset CMS and predominant limb girdle weakness.
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Owen D, Töpf A, Preethish-Kumar V, Lorenzoni PJ, Vroling B, Scola RH, Dias-Tosta E, Geraldo A, Polavarapu K, Nashi S, Cox D, Evangelista T, Dawson J, Thompson R, Senderek J, Laurie S, Beltran S, Gut M, Gut I, Nalini A, and Lochmüller H
- Subjects
- Adult, Age of Onset, Child, Female, Humans, Male, Muscle Weakness genetics, Muscle Weakness pathology, Prognosis, Young Adult, Genes, Recessive, Muscular Dystrophies, Limb-Girdle genetics, Muscular Dystrophies, Limb-Girdle pathology, Mutation, Myasthenic Syndromes, Congenital genetics, Myasthenic Syndromes, Congenital pathology, Receptor Protein-Tyrosine Kinases genetics, Receptors, Cholinergic genetics
- Abstract
Congenital myasthenic syndrome (CMS) is a heterogeneous disorder that causes fatigable muscle weakness. CMS has been associated with variants in the MuSK gene and, to date, 16 patients have been reported. MuSK-CMS patients present a different phenotypic pattern of limb girdle weakness. Here, we describe four additional patients and discuss the phenotypic and clinical relationship with those previously reported. Two novel damaging missense variants are described: c.1742T > A; p.I581N found in homozygosis, and c.1634T > C; p.L545P found in compound heterozygosis with p.R166*. The reported patients had predominant limb girdle weakness with symptom onset at 12, 17, 18, and 30 years of age, and the majority exhibited a good clinical response to Salbutamol therapy, but not to esterase inhibitors. Meta-analysis including previously reported variants revealed an increased likelihood of a severe, respiratory phenotype with null alleles. Missense variants exclusively affecting the kinase domain, but not the catalytic site, are associated with late onset. These data refine the phenotype associated with MuSK-related CMS., (© 2018 Wiley Periodicals, Inc.)
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- 2018
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38. How to Spot Congenital Myasthenic Syndromes Resembling the Lambert-Eaton Myasthenic Syndrome? A Brief Review of Clinical, Electrophysiological, and Genetics Features.
- Author
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Lorenzoni PJ, Scola RH, Kay CSK, Werneck LC, Horvath R, and Lochmüller H
- Subjects
- Acetylcholine physiology, Agrin genetics, Autoimmunity, Calcium Signaling, Electrophysiology, Exercise, Exocytosis, Humans, Laminin genetics, Myasthenic Syndromes, Congenital genetics, Nerve Tissue Proteins genetics, Neural Conduction, Neuromuscular Junction physiopathology, SNARE Proteins physiology, Synaptic Transmission, Synaptotagmin II genetics, Vesicle-Associated Membrane Protein 1 genetics, Lambert-Eaton Myasthenic Syndrome diagnosis, Myasthenic Syndromes, Congenital diagnosis
- Abstract
Congenital myasthenic syndromes (CMS) are heterogeneous genetic diseases in which neuromuscular transmission is compromised. CMS resembling the Lambert-Eaton myasthenic syndrome (CMS-LEMS) are emerging as a rare group of distinct presynaptic CMS that share the same electrophysiological features. They have low compound muscular action potential amplitude that increment after brief exercise (facilitation) or high-frequency repetitive nerve stimulation. Although clinical signs similar to LEMS can be present, the main hallmark is the electrophysiological findings, which are identical to autoimmune LEMS. CMS-LEMS occurs due to deficits in acetylcholine vesicle release caused by dysfunction of different components in its pathway. To date, the genes that have been associated with CMS-LEMS are AGRN, SYT2, MUNC13-1, VAMP1, and LAMA5. Clinicians should keep in mind these newest subtypes of CMS-LEMS to achieve the correct diagnosis and therapy. We believe that CMS-LEMS must be included as an important diagnostic clue to genetic investigation in the diagnostic algorithms to CMS. We briefly review the main features of CMS-LEMS.
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- 2018
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39. Late-onset Pompe disease: what is the prevalence of limb-girdle muscular weakness presentation?
- Author
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Lorenzoni PJ, Kay CSK, Higashi NS, D'Almeida V, Werneck LC, and Scola RH
- Subjects
- Adult, Biopsy, Female, Glycogen Storage Disease Type II blood, Glycogen Storage Disease Type II pathology, Humans, Male, Muscular Dystrophies, Limb-Girdle pathology, Prevalence, Glycogen Storage Disease Type II diagnosis, Muscular Dystrophies, Limb-Girdle blood, Muscular Dystrophies, Limb-Girdle diagnosis, alpha-Glucosidases blood
- Abstract
Pompe disease is an inherited disease caused by acid alpha-glucosidase (GAA) deficiency. A single center observational study aimed at assessing the prevalence of late-onset Pompe disease in a high-risk Brazilian population, using the dried blood spot test to detect GAA deficiency as a main screening tool. Dried blood spots were collected for GAA activity assay from 24 patients with "unexplained" limb-girdle muscular weakness without vacuolar myopathy in their muscle biopsy. Samples with reduced enzyme activity were also investigated for GAA gene mutations. Of the 24 patients with dried blood spots, one patient (4.2%) showed low GAA enzyme activity (NaG/AaGIA: 40.42; %INH: 87.22%). In this patient, genetic analysis confirmed two heterozygous mutations in the GAA gene (c.-32-13T>G/p.Arg854Ter). Our data confirm that clinicians should look for late-onset Pompe disease in patients whose clinical manifestation is an "unexplained" limb-girdle weakness even without vacuolar myopathy in muscle biopsy.
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- 2018
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40. Predictors of early left ventricular systolic dysfunction in duchenne muscular dystrophy patients.
- Author
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Cirino RHD, Scola RH, Ducci RD, Wermelinger ACC, Kay CSK, Lorenzoni PJ, Werneck LC, Carmes ER, and Da Cunha CLP
- Abstract
Introduction: Early detection of left ventricular systolic dysfunction (LVSD) is important for therapeutic strategies for Duchenne muscular dystrophy (DMD) patients. We analyzed myocardial strain using echocardiography for early detection of LVSD and determined the predictors of early LVSD., Methods: This investigation was a cross-sectional study of 40 DMD patients with normal left ventricular ejection fraction. Global longitudinal strain (GLS) was used to analyze subtle disturbances in longitudinal contraction of the myocardium. Patients were determined to have early LVSD (GLS > -18) or normal left ventricular systolic function (GLS ≤ -18)., Results: Patients who had early LVSD were older and had a higher frequency of corticosteroid therapy and of mutations in exons 45, 46, 47, 48, 49, 50, and 52., Discussion: Myocardial strain measurements are useful for the early diagnosis of LVSD in DMD patients. Older age, use of corticosteroids, and mutations within the "hot-spot" region of the DMD gene are associated with early LVSD. Muscle Nerve, 2018., (© 2018 Wiley Periodicals, Inc.)
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- 2018
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41. Lambert-Eaton myasthenic syndrome: the 60th anniversary of Eaton and Lambert's pioneering article.
- Author
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Lorenzoni PJ, Kay CSK, Werneck LC, and Scola RH
- Subjects
- Electromyography methods, Electrophysiological Phenomena, History, 20th Century, History, 21st Century, Humans, Lambert-Eaton Myasthenic Syndrome diagnosis, Lambert-Eaton Myasthenic Syndrome physiopathology, Periodicals as Topic, Electromyography history, Lambert-Eaton Myasthenic Syndrome history
- Abstract
This historical review describes the contribution of Drs. Lee M. Eaton and Edward H. Lambert to the diagnosis of myasthenic syndrome on the 60th anniversary of their pioneering article (JAMA 1957) on the disease. There are important landmarks in their article on a disorder of the neuromuscular junction associated with thoracic neoplasm and the electrophysiological criteria for Lambert-Eaton myasthenic syndrome (LEMS). After 60 years, the main electrophysiological criteria described in Eaton and Lambert's pioneering article are still currently useful in the diagnosis of LEMS.
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- 2018
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42. Immune-mediated rippling muscle disease in a patient with treated hypothyroidism.
- Author
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Ducci RD, Scola RH, Lorenzoni PJ, Kay CSK, Blood MRY, Leão LG, Vainzof M, and Werneck LC
- Subjects
- Adolescent, Adrenal Cortex Hormones therapeutic use, Azathioprine therapeutic use, Female, Humans, Hypothyroidism immunology, Hypothyroidism pathology, Immunologic Factors therapeutic use, Muscular Diseases pathology, Muscular Diseases therapy, Hypothyroidism complications, Hypothyroidism therapy, Muscular Diseases complications, Muscular Diseases immunology
- Published
- 2017
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43. Treatment of epilepsy in patients with myasthenia gravis: Is really harder than it looks?
- Author
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Lorenzoni PJ, Ducci RD, Tensini TS, Dalledone G, Kay CSK, de Paola L, Werneck LC, Scola RH, and Silvado C
- Subjects
- Adult, Epilepsy drug therapy, Epilepsy surgery, Female, Humans, Myasthenia Gravis drug therapy, Myasthenia Gravis surgery, Anterior Temporal Lobectomy, Anticonvulsants therapeutic use, Epilepsy complications, Epilepsy therapy, Myasthenia Gravis complications, Myasthenia Gravis therapy
- Abstract
The relationship between myasthenia gravis (MG) and epilepsy has been rarely reported. As consequence, there are no specific guidelines for the management of these conditions when they mutually occur. We reported on three patients in whom epilepsy and MG are coexisting, but in different clinical settings. Two patients were treated with antiepileptic drugs which improved their symptoms. One patient has controlled the seizures after a successful anterior temporal lobectomy with no appreciable consequences to her MG. We discuss the difficulties in the management of epilepsy in patients with MG. In addition, we report on the first epileptic surgery in a MG patient, indicating that this surgical procedure as a safe option for the treatment of intractable epilepsy in patients with MG., (Copyright © 2017. Published by Elsevier Ltd.)
- Published
- 2017
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44. Is there a relationship between narcolepsy, multiple sclerosis and HLA-DQB1*06:02?
- Author
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Lorenzoni PJ, Werneck LC, Crippa ACS, Zanatta A, Kay CSK, Silvado CES, and Scola RH
- Subjects
- Adult, Aged, Female, Gene Frequency, Genotype, Humans, Male, Middle Aged, Multiple Sclerosis genetics, Narcolepsy diagnosis, Narcolepsy genetics, Polysomnography, Young Adult, HLA-DQ beta-Chains genetics, Multiple Sclerosis complications, Narcolepsy etiology
- Abstract
We studied multiple sclerosis (MS) patients with the HLA-DQB1*06:02 allele and compared them with MS patients who did not carry the HLA-DQB1*06:02 allele. We analyzed clinical and neurophysiological criteria for narcolepsy in six MS patients with HLA-DQB1*06:02, compared with 12 MS patients who were HLA-DQB1*06:02 non-carriers. Only two patients with HLA-DQB1*06:02 allele scored higher than 10 on the Epworth Sleepiness Scale. Polysomnography recording parameters and the multiple sleep latency test showed an absence of narcolepsy in the study group. Our study suggested no significant correlation between narcolepsy, MS and HLA-DQB1*06:02. The HLA-DQB1*06:02 allele alone was not sufficient to cause MS patients to develop narcolepsy.
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- 2017
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45. Intragenic DOK7 deletion detected by whole-genome sequencing in congenital myasthenic syndromes.
- Author
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Azuma Y, Töpf A, Evangelista T, Lorenzoni PJ, Roos A, Viana P, Inagaki H, Kurahashi H, and Lochmüller H
- Abstract
Objective: To identify the genetic cause in a patient affected by ptosis and exercise-induced muscle weakness and diagnosed with congenital myasthenic syndromes (CMS) using whole-genome sequencing (WGS)., Methods: Candidate gene screening and WGS analysis were performed in the case. Allele-specific PCR was subsequently performed to confirm the copy number variation (CNV) that was suspected from the WGS results., Results: In addition to the previously reported frameshift mutation c.1124_1127dup, an intragenic 6,261 bp deletion spanning from the 5' untranslated region to intron 2 of the DOK7 gene was identified by WGS in the patient with CMS. The heterozygous deletion was suspected based on reduced coverage on WGS and confirmed by allele-specific PCR. The breakpoints had microhomology and an inverted repeat, which may have led to the development of the deletion during DNA replication., Conclusions: We report a CMS case with identification of the breakpoints of the intragenic DOK7 deletion using WGS analysis. This case illustrates that CNVs undetected by Sanger sequencing may be identified by WGS and highlights their relevance in the molecular diagnosis of a treatable neurologic condition such as CMS.
- Published
- 2017
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46. Clinical follow-up of pregnancy in myasthenia gravis patients.
- Author
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Ducci RD, Lorenzoni PJ, Kay CS, Werneck LC, and Scola RH
- Subjects
- Adult, Female, Fetal Membranes, Premature Rupture diagnosis, Fetal Membranes, Premature Rupture epidemiology, Follow-Up Studies, Humans, Myasthenia Gravis epidemiology, Pregnancy, Pregnancy Complications epidemiology, Young Adult, Myasthenia Gravis diagnosis, Pregnancy Complications diagnosis
- Abstract
This study aimed to analyze the outcome and impact of pregnancy in women with myasthenia gravis (MG). Obstetric and clinical data were retrospectively analyzed before, during and after pregnancy. Predictors of outcome were studied. We included 35 pregnancies from 21 MG patients. In the course of MG symptoms in 30 pregnancies with live births, 50% deteriorated (mainly during the second trimester, p = 0.028), 30% improved, and 20% remained unchanged. The deterioration group had more frequent abnormal repetitive nerve stimulation (RNS) (p = 0.028) and lower myasthenia gravis composite (MGC) scores (p = 0.045) before pregnancy. The improvement group was associated with higher MGC scores (p = 0.012) before pregnancy. The no-change group was associated with longer duration of MG (p = 0.026) and normal RNS (p = 0.008) before pregnancy. The course of MG in the second pregnancy was different from that in the previous pregnancy in 65.3% of cases. Obstetric complications were reported in 20 pregnancies; the most common was preterm premature rupture of membranes (PPROM) (25.8%), and the most severe were abortion (11.4%) and fetal death (2.9%). Most of the patients delivered via caesarean section (66.7%). Spinal anesthesia was performed in 73.3%. Transient neonatal myasthenia gravis occurred in 12.9% of live-born infants, and no predictors were found. In conclusion, severity and duration of MG, RNS and treatment influence MG and pregnancy. Pregnant MG patients have greater rates of PPROM and caesarean delivery. Our data suggest that duration of MG, MGC and RNS before pregnancy may be useful in helping to predict the course of MG during pregnancy., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2017
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47. Novel synaptobrevin-1 mutation causes fatal congenital myasthenic syndrome.
- Author
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Shen XM, Scola RH, Lorenzoni PJ, Kay CS, Werneck LC, Brengman J, Selcen D, and Engel AG
- Abstract
Objective: To identify the molecular basis and elucidate the pathogenesis of a fatal congenital myasthenic syndrome., Methods: We performed clinical electrophysiology studies, exome and Sanger sequencing, and analyzed functional consequences of the identified mutation., Results: Clinical electrophysiology studies of the patient revealed several-fold potentiation of the evoked muscle action potential by high frequency nerve stimulation pointing to a presynaptic defect. Exome sequencing identified a homozygous c.340delA frameshift mutation in synaptobrevin 1 (SYB1), one of the three SNARE proteins essential for synaptic vesicle exocytosis. Analysis of both human spinal cord gray matter and normal human muscle revealed expression of the SYB1A and SYB1D isoforms, predicting expression of one or both isoforms in the motor nerve terminal. The identified mutation elongates the intravesicular C-terminus of the A isoform from 5 to 71, and of the D isoform from 4 to 31 residues. Transfection of either mutant isoform into bovine chromaffin cells markedly reduces depolarization-evoked exocytosis, and transfection of either mutant isoform into HEK cells significantly decreases expression of either mutant compared to wild type., Interpretation: The mutation is pathogenic because elongation of the intravesicular C-terminus of the A and D isoforms increases the energy required to move their C-terminus into the synaptic vesicle membrane, a key step for fusion of the synaptic vesicle with the presynaptic membrane, and because it is predicted to reduce expression of either isoform in the nerve terminal.
- Published
- 2017
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48. Polymyositis without Beneficial Response to Steroid Therapy: Should Miyoshi Myopathy be a Differential Diagnosis?
- Author
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Scalco RS, Lorenzoni PJ, Lynch DS, Martins WA, Jungbluth H, Quinlivan R, Becker J, and Houlden H
- Subjects
- Adolescent, Biomarkers metabolism, Diagnosis, Differential, Disease Progression, Dysferlin, Humans, Male, Muscle, Skeletal pathology, Myalgia genetics, Distal Myopathies diagnosis, Distal Myopathies genetics, Membrane Proteins genetics, Muscle Proteins genetics, Muscular Atrophy diagnosis, Muscular Atrophy genetics, Mutation, Polymyositis diagnosis
- Abstract
BACKGROUND Miyoshi myopathy (MM) is an autosomal-recessive muscle disorder caused by mutations in the DYSF gene. Clinical features and histopathological changes in dysferlinopathies may mimic inflammatory myopathies and a high degree of clinical suspicion is required to guide the genetic investigation. CASE REPORT We report the case of a 16-year-old male who presented with severe bilateral calf pain and elevated CK levels (15 000 IU/l) who was on prolonged steroid therapy prompted by the clinical suspicion of inflammatory myopathy. Three years into his illness, he was referred for neuromuscular evaluation presenting with untreatable muscle pain and progressive weakness. The diagnosis of "refractory polymyositis" was revisited. Targeted exome sequencing revealed homozygous pathogenic mutations in the DYSF gene, confirming a diagnosis of Miyoshi myopathy. CONCLUSIONS Our case illustrates that severe muscle pain may be the initial feature of Miyoshi myopathy and should be considered in the differential diagnosis of inflammatory myopathies. Although the described patient reported partial clinical improvement in muscle pain, steroid treatment is not an effective therapy for dysferlinopathy patients and it did not prevent disease progression. In addition, we confirm the utility of next-generation sequencing approaches to myopathies, particularly in complex or unusual cases when muscle biopsy is not available., Competing Interests: Conflicts of Interest: None declared
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- 2017
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49. Hereditary Neuropathy With Liability to Pressure Palsies: A Single-Center Experience in Southern Brazil.
- Author
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Lorenzoni PJ, Kay CS, Cavalet C, Arndt RC, Werneck LC, and Scola RH
- Abstract
The spectrum of clinical and electrophysiological features in hereditary neuropathy with liability to pressure palsies (HNPP) is broad. We analyze a series of Brazilian patients with HNPP. Correlations between clinical manifestations, laboratory features, electrophysiological analyze, histological and molecular findings were done. In five cases, more than one episode occurred before diagnosis. Median nerve in the carpal tunnel at the wrist, ulnar nerve in its groove at the elbow, fibular nerve in the head of the fibula at the knee, radial nerve in its groove of the humerus and suprascapular nerve in its notch at the supraspinous fossa were found as focal neuropathies. One patient presented with persistent writer's cramp after ulnar nerve palsy. Nerve conduction studies showed focal neuropathy in all patients and concomitant generalized symmetrical neuropathy in eight patients. Molecular analysis of the PMP22 gene detected deletion of the 1.5-Mb fragment in all patients., Competing Interests: the authors declare no potential conflict of interest.
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- 2016
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50. Necrotizing myopathy: An uncommon initial manifestation of human immunodeficiency virus.
- Author
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Ducci RD, de Magalhães FB, Collares D, Lorenzoni PJ, Gomes-da-Silva MM, Kay CS, Carvalho M, Werneck LC, and Scola RH
- Subjects
- Diagnosis, Differential, HIV Infections blood, Humans, Male, Muscular Diseases blood, Necrosis, Young Adult, HIV Infections complications, HIV Infections diagnosis, Muscular Diseases complications, Muscular Diseases diagnosis, Quadriceps Muscle pathology
- Published
- 2016
- Full Text
- View/download PDF
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