21 results on '"García Sobrino, T."'
Search Results
2. Successful treatment of hypokalemic periodic paralysis with topiramate
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García-Sobrino, T. and Pardo, J.
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- 2014
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3. VAGUS NERVE STIMULATION DECREASE EMERGENCY ASSISTANCE AND HOSPITALIZATION IN DRUG-RESSISTANT EPILEPTIC PATIENS: p370
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García-Sobrino, T., Rodríguez-Osorio, X., López-Ferreiro, A., Santamaría-Cadavid, M., Corredera, E., Prieto, A., Peleteiro, M., and López-González, F. J.
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- 2012
4. EPILEPTC APHASIA: A DESCRIPTION OF 10 NEW CASES: p319
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López-Ferreiro, A., Rodríguez-Osorio, X., Fernández-Ferro, J. C., García-Sobrino, T., Rodríguez-Yañez, M., Arias, M., Pardo, J., Corredera, E., and López-Gonzălez, F. J.
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- 2012
5. Distal myasthenia simulating radial nerve palsy: A case report.
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Anonymous, García-Sobrino, T., Vidal, M.P., Pardo-Parrado, M., Fernández-Pajarín, G., and Santamaría-Cadavid, M.
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- 2013
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6. Clinical practice guidelines for the diagnosis and management of Charcot-Marie-Tooth disease
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Sivera Mascaró, R., García Sobrino, T., Horga Hernández, A., Pelayo Negro, A.L., Alonso Jiménez, A., Antelo Pose, A., Calabria Gallego, M.D., Casasnovas, C., Cemillán Fernández, C.A., Esteban Pérez, J., Fenollar Cortés, M., Frasquet Carrera, M., Gallano Petit, M.P., Giménez Muñoz, A., Gutiérrez Gutiérrez, G., Gutiérrez Martínez, A., Juntas Morales, R., Ciano-Petersen, N.L., Martínez Ulloa, P.L., Mederer Hengstl, S., Millet Sancho, E., Navacerrada Barrero, F.J., Navarrete Faubel, F.E., Pardo Fernández, J., Pascual Pascual, S.I., Pérez Lucas, J., Pino Mínguez, J., Rabasa Pérez, M., Sánchez González, M., Sotoca, J., Rodríguez Santiago, B., Rojas García, R., Turon-Sans, J., Vicent Carsí, V., and Sevilla Mantecón, T.
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7. Clinical and neuroimaging features of familial C9FTD/ALS: A case report.
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Anonymous, Pardo-Parrado, M., Clarimón, J., García-Redondo, A., Cebrián, E., Jiménez-Martínez, I., Cortés, J., Aguiar, P., Castiñeiras, J.A., García-Sobrino, T., Quintáns, B., and Sobrido, M.J.
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- 2013
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8. Clinical practice guidelines for the diagnosis and management of Charcot-Marie-Tooth disease.
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Sivera Mascaró R, García Sobrino T, Horga Hernández A, Pelayo Negro AL, Alonso Jiménez A, Antelo Pose A, Calabria Gallego MD, Casasnovas C, Cemillán Fernández CA, Esteban Pérez J, Fenollar Cortés M, Frasquet Carrera M, Gallano Petit MP, Giménez Muñoz A, Gutiérrez Gutiérrez G, Gutiérrez Martínez A, Juntas Morales R, Ciano-Petersen NL, Martínez Ulloa PL, Mederer Hengstl S, Millet Sancho E, Navacerrada Barrero FJ, Navarrete Faubel FE, Pardo Fernández J, Pascual Pascual SI, Pérez Lucas J, Pino Mínguez J, Rabasa Pérez M, Sánchez González M, Sotoca J, Rodríguez Santiago B, Rojas García R, Turon-Sans J, Vicent Carsí V, and Sevilla Mantecón T
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Introduction: Charcot-Marie-Tooth disease (CMT) is classified according to neurophysiological and histological findings, the inheritance pattern, and the underlying genetic defect. The objective of these guidelines is to offer recommendations for the diagnosis, prognosis, follow-up, and treatment of this disease in Spain., Material and Methods: These consensus guidelines were developed through collaboration by a multidisciplinary panel encompassing a broad group of experts on the subject, including neurologists, paediatric neurologists, geneticists, physiatrists, and orthopaedic surgeons., Recommendations: The diagnosis of CMT is clinical, with patients usually presenting a common or classical phenotype. Clinical assessment should be followed by an appropriate neurophysiological study; specific recommendations are established for the parameters that should be included. Genetic diagnosis should be approached sequentially; once PMP22 duplication has been ruled out, if appropriate, a next-generation sequencing study should be considered, taking into account the limitations of the available techniques. To date, no pharmacological disease-modifying treatment is available, but symptomatic management, guided by a multidiciplinary team, is important, as is proper rehabilitation and orthopaedic management. The latter should be initiated early to identify and improve the patient's functional deficits, and should include individualised exercise guidelines, orthotic adaptation, and assessment of conservative surgeries such as tendon transfer. The follow-up of patients with CMT is exclusively clinical, and ancillary testing is not necessary in routine clinical practice., (Copyright © 2024 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)
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- 2024
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9. [Epidemiology of myasthenia gravis in the Iberian Peninsula and Latin America].
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García-Estévez DA, Fraga-Bau A, García-Sobrino T, Mederer-Hengstl S, and Pardo-Fernández J
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- Aged, Male, Female, Humans, Latin America epidemiology, Age Distribution, Epidemiologic Studies, Incidence, Myasthenia Gravis epidemiology
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Introduction: Although today we live in a globalised world, the ties established between the Iberian Peninsula and the countries of Latin America are particularly strong, with important migratory flows. This connection may condition the development of diseases that involve a genetic influence, which may in turn be modulated by various environmental factors. The aim of this review is to determine the descriptive epidemiology of myasthenia gravis in the Iberian Peninsula and in Latin America., Development: A literature search was conducted in Medline, LILACS and Google Scholar for the different countries of interest using the terms 'prevalence', 'incidence', 'epidemiology' and 'myasthenia gravis'. The methodology and quality were reviewed, and descriptive data about the study population as well as data on prevalence were extracted., Conclusions: Many countries lack epidemiological studies on myasthenia gravis and in others the data reported focus on one referral hospital, making it difficult to compare prevalence between countries. In the Iberian Peninsula, the prevalence is consistently above 100 cases x 106 inhabitants, the highest figures being found in the area of Osona (Barcelona) and in the province of Ourense. In Latin America, much lower prevalence figures are reported, generally below 100 x 106 inhabitants. There is a predominance of females in the early-onset forms (<50 years) and a clear increase in prevalence in the elderly population, especially in the very late onset forms (>65 years), where it is more frequent in men.
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- 2023
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10. Characterizing SOD1 mutations in Spain. The impact of genotype, age, and sex in the natural history of the disease.
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Vázquez-Costa JF, Borrego-Hernández D, Paradas C, Gómez-Caravaca MT, Rojas-Garcia R, Varona L, Povedano M, García-Sobrino T, Jericó Pascual I, Gutiérrez A, Riancho J, Turon-Sans J, Assialioui A, Pérez-Tur J, Sevilla T, Esteban Pérez J, and García-Redondo A
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Introduction: The aim of this study is to describe the frequency and distribution of SOD1 mutations in Spain, and to explore those factors contributing to their phenotype and prognosis., Methods: Seventeen centres shared data on amyotrophic lateral sclerosis (ALS) patients carrying pathogenic or likely pathogenic SOD1 variants. Multivariable models were used to explore prognostic modifiers., Results: In 144 patients (from 88 families), 29 mutations (26 missense, 2 deletion/insertion and 1 frameshift) were found in all 5 exons of SOD1, including 7 novel mutations. 2.6% of ALS patients (including 17.7% familial and 1.3% sporadic) were estimated to carry SOD1 mutations. Its frequency varied considerably between regions, due to founder events. The most frequent mutation was p.Gly38Arg (n = 58), followed by p.Glu22Gly (n = 11), p.Asn140His (n = 10), and the novel p.Leu120Val (n = 10). Most mutations were characterized by a protracted course, and some of them by atypical phenotypes. Older age of onset was independently associated with faster disease progression (exp(Estimate) = 1.03 [0.01, 0.05], p = 0.001) and poorer survival (HR = 1.05 [1.01, 1.08], p = 0.007), regardless of the underlying mutation. Female sex was independently associated to faster disease progression (exp(Estimate) = 2.1 [1.23, 3.65], p = 0.012) in patients carrying the p.Gly38Arg mutation, resulting in shorter survival compared with male carriers (236 vs 301 months)., Conclusions: These data may help to evaluate the efficacy of SOD1 targeted treatments, and to expand the number of patients that might benefit from these treatments., (This article is protected by copyright. All rights reserved.)
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- 2022
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11. Autoantibody screening in Guillain-Barré syndrome.
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Lleixà C, Martín-Aguilar L, Pascual-Goñi E, Franco T, Caballero M, de Luna N, Gallardo E, Suárez-Calvet X, Martínez-Martínez L, Diaz-Manera J, Rojas-García R, Cortés-Vicente E, Turón J, Casasnovas C, Homedes C, Gutiérrez-Gutiérrez G, Jimeno-Montero MC, Berciano J, Sedano-Tous MJ, García-Sobrino T, Pardo-Fernández J, Márquez-Infante C, Rojas-Marcos I, Jericó-Pascual I, Martínez-Hernández E, Morís de la Tassa G, Domínguez-González C, Juárez C, Illa I, and Querol L
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- Aged, Animals, Cell Line, Tumor, Cohort Studies, Female, Ganglia, Spinal metabolism, Ganglia, Spinal pathology, Guillain-Barre Syndrome epidemiology, Humans, Macaca, Male, Mass Screening methods, Middle Aged, Prospective Studies, Rats, Spain epidemiology, Autoantibodies blood, Guillain-Barre Syndrome blood, Guillain-Barre Syndrome diagnosis
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Background: Guillain-Barré syndrome (GBS) is an acute inflammatory neuropathy with a heterogeneous presentation. Although some evidences support the role of autoantibodies in its pathogenesis, the target antigens remain unknown in a substantial proportion of GBS patients. The objective of this study is to screen for autoantibodies targeting peripheral nerve components in Guillain-Barré syndrome., Methods: Autoantibody screening was performed in serum samples from all GBS patients included in the International GBS Outcome study by 11 different Spanish centres. The screening included testing for anti-ganglioside antibodies, anti-nodo/paranodal antibodies, immunocytochemistry on neuroblastoma-derived human motor neurons and murine dorsal root ganglia (DRG) neurons, and immunohistochemistry on monkey peripheral nerve sections. We analysed the staining patterns of patients and controls. The prognostic value of anti-ganglioside antibodies was also analysed., Results: None of the GBS patients (n = 100) reacted against the nodo/paranodal proteins tested, and 61 (61%) were positive for, at least, one anti-ganglioside antibody. GBS sera reacted strongly against DRG neurons more frequently than controls both with IgG (6% vs 0%; p = 0.03) and IgM (11% vs 2.2%; p = 0.02) immunodetection. No differences were observed in the proportion of patients reacting against neuroblastoma-derived human motor neurons. Reactivity against monkey nerve tissue was frequently detected both in patients and controls, but specific patterns were only detected in GBS patients: IgG from 13 (13%) patients reacted strongly against Schwann cells. Finally, we confirmed that IgG anti-GM1 antibodies are associated with poorer outcomes independently of other known prognostic factors., Conclusion: Our study confirms that (1) GBS patients display a heterogeneous repertoire of autoantibodies targeting nerve cells and structures; (2) gangliosides are the most frequent antigens in GBS patients and have a prognostic value; (3) further antigen-discovery experiments may elucidate other potential antigens in GBS., (© 2021. The Author(s).)
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- 2021
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12. Charcot-Marie-Tooth disease due to MORC2 mutations in Spain.
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Sivera R, Lupo V, Frasquet M, Argente-Escrig H, Alonso-Pérez J, Díaz-Manera J, Querol L, Del Mar García-Romero M, Ignacio Pascual S, García-Sobrino T, Paradas C, Francisco Vázquez-Costa J, Muelas N, Millet E, Jesús Vílchez J, Espinós C, and Sevilla T
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- Humans, Mutation, Phenotype, Retrospective Studies, Spain epidemiology, Transcription Factors, Charcot-Marie-Tooth Disease epidemiology, Charcot-Marie-Tooth Disease genetics
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Background and Purpose: MORC2 mutations have been described as a rare cause of axonal Charcot-Marie-Tooth disease (CMT2Z). The aim of this work was to determine the frequency and distribution of these mutations throughout Spain, to provide a comprehensive phenotypical description and, if possible, to establish a genotype-phenotype correlation., Methods: Retrospectively, data on patients diagnosed with CMT2Z in Spain were collected and clinical, electrophysiological and muscle imaging information were analysed., Results: Fifteen patients with CMT2Z were identified throughout Spain, seven of them belonging to a single kindred, whilst the rest were sporadic. The most common mutation was p.R252W, and four new mutations were identified. Eleven patients were categorized as having a scapuloperoneal phenotype, with asymmetric muscle weakness, early proximal upper limb involvement and frequent spontaneous muscular activity with distal sensory impairment and pes cavus, whilst two presented with a more classic length dependent sensory motor phenotype. This distinction was corroborated by the distribution of muscle fatty infiltration in muscle imaging. Two other patients were classified as having a neurodevelopmental phenotype consisting in congenital or early onset, delay in motor milestones, and global developmental delay in one of them. Nerve conduction studies revealed an unequivocally axonal neuropathy with frequent spontaneous activity, and serum creatine kinase levels were increased in 50% of the patients., Conclusions: MORC2 mutations are a rare cause of CMT in Spain, but in-depth phenotyping reveals a recognizable phenotypic spectrum that will be clinically relevant for future identification of this disease., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)
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- 2021
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13. Serum neurofilament light chain predicts long-term prognosis in Guillain-Barré syndrome patients.
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Martín-Aguilar L, Camps-Renom P, Lleixà C, Pascual-Goñi E, Díaz-Manera J, Rojas-García R, De Luna N, Gallardo E, Cortés-Vicente E, Muñoz L, Alcolea D, Lleó A, Casasnovas C, Homedes C, Gutiérrez-Gutiérrez G, Jimeno-Montero MC, Berciano J, Sedano-Tous MJ, García-Sobrino T, Pardo-Fernández J, Márquez-Infante C, Rojas-Marcos I, Jericó-Pascual I, Martínez-Hernández E, Morís de la Tassa G, Domínguez-González C, Illa I, and Querol L
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Objective: To study baseline serum neurofilament light chain (sNfL) levels as a prognostic biomarker in Guillain-Barré syndrome (GBS)., Methods: We measured NfL in serum (98 samples) and cerebrospinal fluid (CSF) (24 samples) of patients with GBS prospectively included in the International GBS Outcome Study (IGOS) in Spain using single-molecule array (SiMoA) and compared them with 53 healthy controls (HCs). We performed multivariable regression to analyse the association between sNfL levels and functional outcome at 1 year., Results: Patients with GBS had higher NfL levels than HC in serum (55.49 pg/mL vs 9.83 pg/mL, p<0.0001) and CSF (1308.5 pg/mL vs 440.24 pg/mL, p=0.034). Patients with preceding diarrhoea had higher sNfL than patients with respiratory symptoms or no preceding infection (134.90 pg/mL vs 47.86 pg/mL vs 38.02 pg/mL, p=0.016). sNfL levels correlated with Guillain-Barré Syndrome Disability Score and Inflammatory Rasch-built Overall Disability Scale (I-RODS) at every timepoint. Patients with pure motor variant and Miller Fisher syndrome showed higher sNfL levels than patients with sensorimotor GBS (162.18 pg/mL vs 95.50 pg/mL vs 38.02 pg/mL, p=0.025). Patients with acute motor axonal neuropathy cute motor axonal neuropathy had higher sNfL levels than other variants (190.55 pg/mL vs 46.79 pg/mL, p=0.013). sNfL returned to normal levels at 1 year. High baseline sNfL levels were associated with inability to run (OR=1.65, 95% CI 1.14 to 2.40, p=0.009) and lower I-RODS (β -2.60, 95% CI -4.66 to -0.54, p=0.014) at 1 year. Cut-off points predicting clinically relevant outcomes at 1 year with high specificity were calculated: inability to walk independently (>319 pg/mL), inability to run (>248 pg/mL) and ability to run (<34 pg/mL)., Conclusion: Baseline sNfL levels are increased in patients with GBS, are associated with disease severity and axonal variants and have an independent prognostic value in patients with GBS., Competing Interests: Competing interests: LAQ has provided expert testimony for Grifols, Sanofi-Genzyme, Novartis, UCB, Roche and CSL Behring and received research funds from Novartis Spain, Sanofi-Genzyme and Grifols. LM-A has received speaking honoraria from Roche. EP-G has received speaking honoraria from Roche and Biogen. JD-M has provided expert testimony for PTC and Sanofi-Genzyme, has been external advisor for Sanofi, Sarepta and Audentes and received research funds from Sanofi-Genzyme and Boehringer. DA participated in advisory boards from Fujirebio-Europe and Roche Diagnostics and received speaker honoraria from Fujirebio-Europe, Nutricia and from Krka Farmacéutica S.L. GG-G has received speaking honoraria from Sanofi-Genzyme, Takeda and has provided expert testimony for Biogen and CSL Behring. The other authors report no disclosures., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2020
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14. Chimeric Peptide Species Contribute to Divergent Dipeptide Repeat Pathology in c9ALS/FTD and SCA36.
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McEachin ZT, Gendron TF, Raj N, García-Murias M, Banerjee A, Purcell RH, Ward PJ, Todd TW, Merritt-Garza ME, Jansen-West K, Hales CM, García-Sobrino T, Quintáns B, Holler CJ, Taylor G, San Millán B, Teijeira S, Yamashita T, Ohkubo R, Boulis NM, Xu C, Wen Z, Streichenberger N, Fogel BL, Kukar T, Abe K, Dickson DW, Arias M, Glass JD, Jiang J, Tansey MG, Sobrido MJ, Petrucelli L, Rossoll W, and Bassell GJ
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- Amino Acid Sequence, Animals, Animals, Newborn, Antisense Elements (Genetics) genetics, DNA Repeat Expansion, Female, Humans, Introns genetics, Mice, Mice, Inbred C57BL, Pregnancy, Repetitive Sequences, Nucleic Acid, Amyotrophic Lateral Sclerosis genetics, C9orf72 Protein genetics, Dipeptides genetics, Frontotemporal Dementia genetics, Mutant Chimeric Proteins genetics, Spinocerebellar Ataxias genetics
- Abstract
GGGGCC hexanucleotide repeat expansions (HREs) in C9orf72 cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and lead to the production of aggregating dipeptide repeat proteins (DPRs) via repeat associated non-AUG (RAN) translation. Here, we show the similar intronic GGCCTG HREs that causes spinocerebellar ataxia type 36 (SCA36) is also translated into DPRs, including poly(GP) and poly(PR). We demonstrate that poly(GP) is more abundant in SCA36 compared to c9ALS/FTD patient tissue due to canonical AUG-mediated translation from intron-retained GGCCTG repeat RNAs. However, the frequency of the antisense RAN translation product poly(PR) is comparable between c9ALS/FTD and SCA36 patient samples. Interestingly, in SCA36 patient tissue, poly(GP) exists as a soluble species, and no TDP-43 pathology is present. We show that aggregate-prone chimeric DPR (cDPR) species underlie the divergent DPR pathology between c9ALS/FTD and SCA36. These findings reveal key differences in translation, solubility, and protein aggregation of DPRs between c9ALS/FTD and SCA36., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)
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- 2020
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15. Clinical and therapeutic features of myasthenia gravis in adults based on age at onset.
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Cortés-Vicente E, Álvarez-Velasco R, Segovia S, Paradas C, Casasnovas C, Guerrero-Sola A, Pardo J, Ramos-Fransi A, Sevilla T, López de Munain A, Gómez MT, Jericó I, Gutiérrez-Gutiérrez G, Pelayo-Negro AL, Martín MA, Mendoza MD, Morís G, Rojas-Garcia R, Díaz-Manera J, Querol L, Gallardo E, Vélez B, Albertí MA, Galán L, García-Sobrino T, Martínez-Piñeiro A, Lozano-Veintimilla A, Fernández-Torrón R, Cano-Abascal Á, and Illa I
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- Adult, Age of Onset, Aged, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Treatment Outcome, Myasthenia Gravis complications, Myasthenia Gravis drug therapy, Myasthenia Gravis immunology
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Objective: To describe the characteristics of patients with very-late-onset myasthenia gravis (MG)., Methods: This observational cross-sectional multicenter study was based on information in the neurologist-driven Spanish Registry of Neuromuscular Diseases (NMD-ES). All patients were >18 years of age at onset of MG and onset occurred between 2000 and 2016 in all cases. Patients were classified into 3 age subgroups: early-onset MG (age at onset <50 years), late-onset MG (onset ≥50 and <65 years), and very-late-onset MG (onset ≥65 years). Demographic, immunologic, clinical, and therapeutic data were reviewed., Results: A total of 939 patients from 15 hospitals were included: 288 (30.7%) had early-onset MG, 227 (24.2%) late-onset MG, and 424 (45.2%) very-late-onset MG. The mean follow-up was 9.1 years (SD 4.3). Patients with late onset and very late onset were more frequently men ( p < 0.0001). Compared to the early-onset and late-onset groups, in the very-late-onset group, the presence of anti-acetylcholine receptor (anti-AChR) antibodies ( p < 0.0001) was higher and fewer patients had thymoma ( p < 0.0001). Late-onset MG and very-late-onset MG groups more frequently had ocular MG, both at onset (<0.0001) and at maximal worsening ( p = 0.001). Although the very-late-onset group presented more life-threatening events (Myasthenia Gravis Foundation of America IVB and V) at onset ( p = 0.002), they required fewer drugs ( p < 0.0001) and were less frequently drug-refractory ( p < 0.0001)., Conclusions: Patients with MG are primarily ≥65 years of age with anti-AChR antibodies and no thymoma. Although patients with very-late-onset MG may present life-threatening events at onset, they achieve a good outcome with fewer immunosuppressants when diagnosed and treated properly., (© 2020 American Academy of Neurology.)
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- 2020
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16. Muscle MRI in a large cohort of patients with oculopharyngeal muscular dystrophy.
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Alonso-Jimenez A, Kroon RHMJM, Alejaldre-Monforte A, Nuñez-Peralta C, Horlings CGC, van Engelen BGM, Olivé M, González L, Verges-Gil E, Paradas C, Márquez C, Garibaldi M, Gallano P, Rodriguez MJ, Gonzalez-Quereda L, Dominguez Gonzalez C, Vissing J, Fornander F, Eisum AV, García-Sobrino T, Pardo J, García-Figueiras R, Muelas N, Vilchez JJ, Kapetanovic S, Tasca G, Monforte M, Ricci E, Gomez MT, Bevilacqua JA, Diaz-Jara J, Zamorano II, Carlier RY, Laforet P, Pelayo-Negro A, Ramos-Fransi A, Martínez A, Marini-Bettolo C, Straub V, Gutiérrez G, Stojkovic T, Martín MA, Morís G, Fernández-Torrón R, Lopez De Munaín A, Cortes-Vicente E, Querol L, Rojas-García R, Illa I, and Diaz-Manera J
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- Adult, Cohort Studies, Cross-Sectional Studies, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Muscle, Skeletal pathology, Muscular Dystrophy, Oculopharyngeal complications, Muscular Dystrophy, Oculopharyngeal pathology, Tomography, X-Ray Computed, Muscle, Skeletal diagnostic imaging, Muscular Dystrophy, Oculopharyngeal diagnostic imaging
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Background and Objective: Oculopharyngeal muscular dystrophy (OPMD) is a genetic disorder caused by an abnormal expansion of GCN triplets within the PABPN1 gene. Previous descriptions have focused on lower limb muscles in small cohorts of patients with OPMD, but larger imaging studies have not been performed. Previous imaging studies have been too small to be able to correlate imaging findings to genetic and clinical data., Methods: We present cross-sectional, T1-weighted muscle MRI and CT-scan data from 168 patients with genetically confirmed OPMD. We have analysed the pattern of muscle involvement in the disease using hierarchical analysis and presented it as heatmaps. Results of the scans were correlated with genetic and clinical data., Results: Fatty replacement was identified in 96.7% of all symptomatic patients. The tongue, the adductor magnus and the soleus were the most commonly affected muscles. Muscle pathology on MRI correlated positively with disease duration and functional impairment., Conclusions: We have described a pattern that can be considered characteristic of OPMD. An early combination of fat replacement in the tongue, adductor magnus and soleus can be helpful for differential diagnosis. The findings suggest the natural history of the disease from a radiological point of view. The information generated by this study is of high diagnostic value and important for clinical trial development., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2019
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17. Characterising the phenotype and mode of inheritance of patients with inherited peripheral neuropathies carrying MME mutations.
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Lupo V, Frasquet M, Sánchez-Monteagudo A, Pelayo-Negro AL, García-Sobrino T, Sedano MJ, Pardo J, Misiego M, García-García J, Sobrido MJ, Martínez-Rubio MD, Chumillas MJ, Vílchez JJ, Vázquez-Costa JF, Espinós C, and Sevilla T
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- Adult, Aged, Alleles, Amino Acid Substitution, Electromyography, Electrophysiological Phenomena, Female, Gene Frequency, Genes, Recessive, Genotype, Humans, Magnetic Resonance Imaging, Male, Metalloendopeptidases metabolism, Middle Aged, Pedigree, Genetic Association Studies, Inheritance Patterns, Metalloendopeptidases genetics, Mutation, Peripheral Nervous System Diseases diagnosis, Peripheral Nervous System Diseases genetics, Phenotype
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Background: Mutations in the metalloendopeptidase ( MME ) gene were initially identified as a cause of autosomal recessive Charcot-Marie-Tooth disease type 2 (CMT2). Subsequently, variants in MME were linked to other late-onset autosomal dominant polyneuropathies. Thus, our goal was to define the phenotype and mode of inheritance of patients carrying changes in MME ., Methods: We screened 197 index cases with a hereditary neuropathy of the CMT type or distal hereditary motor neuropathy (dHMN) and 10 probands with familial amyotrophic lateral sclerosis (fALS) using a custom panel of 119 genes. In addition to the index case subjects, we also studied other clinically and/or genetically affected and unaffected family members., Results: We found 17 variants in MME in a total of 20 index cases, with biallelic MME mutations detected in 13 cases from nine families (three in homozygosis and six in compound heterozygosis) and heterozygous variants found in 11 families. All patients with biallelic variants had a similar phenotype, consistent with late-onset axonal neuropathy. Conversely, the phenotype of patients carrying heterozygous mutations was highly variable [CMT type 1 (CMT1), CMT2, dHMN and fALS] and mutations did not segregate with the disease., Conclusion: MME mutations that segregate in an autosomal recessive pattern are associated with a late-onset CMT2 phenotype, yet we could not demonstrate that MME variants in heterozygosis cause neuropathy. Our data highlight the importance of establishing an accurate genetic diagnosis in patients carrying MME mutations, especially with a view to genetic counselling., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2018
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18. Distribution and genotype-phenotype correlation of GDAP1 mutations in Spain.
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Sivera R, Frasquet M, Lupo V, García-Sobrino T, Blanco-Arias P, Pardo J, Fernández-Torrón R, de Munain AL, Márquez-Infante C, Villarreal L, Carbonell P, Rojas-García R, Segovia S, Illa I, Frongia AL, Nascimento A, Ortez C, García-Romero MDM, Pascual SI, Pelayo-Negro AL, Berciano J, Guerrero A, Casasnovas C, Camacho A, Esteban J, Chumillas MJ, Barreiro M, Díaz C, Palau F, Vílchez JJ, Espinós C, and Sevilla T
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- Adolescent, Adult, Aged, Charcot-Marie-Tooth Disease metabolism, Child, Child, Preschool, Cross-Sectional Studies, Female, Geography, Medical, Humans, Male, Middle Aged, Retrospective Studies, Spain, Young Adult, Charcot-Marie-Tooth Disease genetics, Genetic Association Studies, Mutation, Nerve Tissue Proteins genetics
- Abstract
Mutations in the GDAP1 gene can cause Charcot-Marie-Tooth disease. These mutations are quite rare in most Western countries but not so in certain regions of Spain or other Mediterranean countries. This cross-sectional retrospective multicenter study analyzed the clinical and genetic characteristics of patients with GDAP1 mutations across Spain. 99 patients were identified, which were distributed across most of Spain, but especially in the Northwest and Mediterranean regions. The most common genotypes were p.R120W (in 81% of patients with autosomal dominant inheritance) and p.Q163X (in 73% of autosomal recessive patients). Patients with recessively inherited mutations had a more severe phenotype, and certain clinical features, like dysphonia or respiratory dysfunction, were exclusively detected in this group. Dominantly inherited mutations had prominent clinical variability regarding severity, including 29% of patients who were asymptomatic. There were minor clinical differences between patients harboring specific mutations but not when grouped according to localization or type of mutation. This is the largest clinical series to date of patients with GDAP1 mutations, and it contributes to define the genetic distribution and genotype-phenotype correlation in this rare form of CMT.
- Published
- 2017
- Full Text
- View/download PDF
19. Phenotypical features of a new dominant GDAP1 pathogenic variant (p.R226del) in axonal Charcot-Marie-Tooth disease.
- Author
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García-Sobrino T, Blanco-Arias P, Palau F, Espinós C, Ramirez L, Estela A, San Millán B, Arias M, Sobrido MJ, and Pardo J
- Subjects
- Adult, Aged, Charcot-Marie-Tooth Disease pathology, DNA Mutational Analysis, Exons genetics, Family Health, Female, HeLa Cells, Humans, Male, Membrane Transport Proteins metabolism, Middle Aged, Mitochondria pathology, Mitochondria ultrastructure, Mitochondrial Precursor Protein Import Complex Proteins, Nerve Tissue Proteins metabolism, Phenotype, Receptors, Cell Surface metabolism, Spain, Sural Nerve metabolism, Transfection, Young Adult, Axons pathology, Charcot-Marie-Tooth Disease genetics, Mutation genetics, Nerve Tissue Proteins genetics
- Abstract
There are few reports on axonal CMT due to dominant GDAP1 mutations. We describe two unrelated Spanish families with a dominant axonal CMT. A novel in frame GAA deletion in exon 5 of the GDAP1 gene (c.677_679del; p.R226del) was identified in both families. Disease onset varied from early childhood to adulthood. Affected family members complained of distal lower limb weakness, cramps and foot deformities with variable CMTNS score in both families. Several individuals were asymptomatic or had paraesthesia only, however neurological examination and nerve conduction studies demonstrated neuropathic signs. Transfection of HeLa cells with the p.R226del mutation led to an increased mitochondrial aggregation. We report an AD-CMT2K with large phenotypic variability due to a novel dominant GDAP1 variant. This is the second founder GDAP1 pathogenic variant reported in Spain., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
20. Gastrointestinal symptoms in late-onset Pompe disease: Early response to enzyme replacement therapy.
- Author
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Pardo J, García-Sobrino T, and López-Ferreiro A
- Subjects
- Humans, Male, Middle Aged, Enzyme Replacement Therapy, Gastrointestinal Diseases etiology, Gastrointestinal Diseases therapy, Glycogen Storage Disease Type II complications, Glycogen Storage Disease Type II therapy
- Published
- 2015
- Full Text
- View/download PDF
21. [Rapidly progressing paraparesis secondary to a fibrosarcoma].
- Author
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García-Sobrino T, Rodríguez-Osorio X, Pardo M, Santamaría-Cadavid M, and Arias M
- Subjects
- Blood Loss, Surgical, Disease Progression, Fatal Outcome, Female, Fibrosarcoma blood supply, Fibrosarcoma diagnostic imaging, Fibrosarcoma pathology, Fibrosarcoma surgery, Hemorrhage etiology, Humans, Middle Aged, Neck Injuries complications, Neoplasm Invasiveness, Radiography, Skin Neoplasms blood supply, Skin Neoplasms diagnostic imaging, Skin Neoplasms pathology, Skin Neoplasms surgery, Subcutaneous Tissue pathology, Thoracic Vertebrae diagnostic imaging, Urinary Incontinence etiology, Fibrosarcoma complications, Paraparesis etiology, Skin Neoplasms complications, Spinal Cord Compression etiology, Thoracic Vertebrae pathology
- Published
- 2014
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