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Resume: Introducción: Las ataxias (AT) y paraparesias espásticas hereditarias (PEH) son síndromes neurodegenerativos raros. Nos proponemos conocer la prevalencia de las AT y PEH en España en 2019. Pacientes y métodos: Estudio transversal, multicéntrico, descriptivo y retrospectivo de los pacientes con AT y PEH, desde marzo de 2018 a diciembre de 2019 en toda España. Resultados: Se obtuvo información de 1933 pacientes procedentes de 11 Comunidades Autónomas, de 47 neurólogos o genetistas. Edad media: 53,64 años ± 20,51 desviación estándar (DE); 938 varones (48,5%), 995 mujeres (51,5%). En 920 pacientes (47,6%) no se conoce el defecto genético. Por patologías, 1.371 pacientes (70,9%) diagnosticados de AT, 562 diagnosticados de PEH (29,1%). La prevalencia estimada de AT es 5,48/100.000 habitantes, y la de PEH es 2,24 casos/100.000 habitantes. La AT dominante más frecuente es la SCA3. La AT recesiva más frecuente es la ataxia de Friedreich (FRDA). La PEH dominante más frecuente es la SPG4, y la PEH recesiva más frecuente es la SPG7. Conclusiones: La prevalencia estimada de AT y PEH en nuestra serie es de 7,73 casos/100.000 habitantes. Estas frecuencias son similares a las del resto del mundo. En el 47,6% no se ha conseguido un diagnóstico genético. A pesar de las limitaciones, este estudio puede contribuir a estimar los recursos, visibilizar estas enfermedades, detectar las mutaciones más frecuentes para hacer los screenings por comunidades, y favorecer los ensayos clínicos. Abstract: Introduction: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. Patients and methods: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. Results: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. Conclusions: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

Introduction: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. Patients and methods: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. Results: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. Conclusions: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials. Resumen: Introducción: Las ataxias (AT) y paraparesias espásticas hereditarias (PEH) son síndromes neurodegenerativos raros. Nos proponemos conocer la prevalencia de las AT y PEH (APEH) en España en 2019. Pacientes y métodos: Estudio transversal, multicéntrico, descriptivo y retrospectivo de los pacientes con AT y PEH, desde Marzo de 2018 a Diciembre de 2019 en toda España. Resultados: Se obtuvo información de 1.933 pacientes procedentes de 11 Comunidades Autónomas, de 47 neurólogos o genetistas. Edad media: 53,64 años ± 20,51 desviación estándar (DE); 938 varones (48,5%), 995 mujeres (51,1%). En 920 pacientes (47,6%) no se conoce el defecto genético. Por patologías, 1.371 pacientes (70,9%) diagnosticados de AT, 562 diagnosticados de PEH (29,1%). La prevalencia estimada de AT es 5,48/100.000 habitantes, y la de PEH es 2,24 casos/100.000 habitantes. La AT dominante más frecuente es la SCA3. La AT recesiva más frecuente es la ataxia de Friedreich (FRDA). La PEH dominante más frecuente es la SPG4, y la PEH recesiva más frecuente es la SPG7. Conclusiones: La prevalencia estimada de APEH en nuestra serie es de 7,73 casos/100.000 habitantes. Estas frecuencias son similares a las del resto del mundo. En el 47,6% no se ha conseguido un diagnóstico genético. A pesar de las limitaciones, este estudio puede contribuir a estimar los recursos, visibilizar estas enfermedades, detectar las mutaciones más frecuentes para hacer los screenings por comunidades, y favorecer los ensayos clínicos.

Introduction: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019., Patients and Methods: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019., Results: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7., Conclusions: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials., (Copyright © 2021 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019., Patients and Methods: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019., Results: We gathered data from a total of 1.809 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 920 patients were men (50.8%) and 889 were women (49.2%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7., Conclusions: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials., (Copyright © 2021 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Myasthenia gravis (MG) is an autoimmune disease caused by antibodies targeting the neuromuscular junction of skeletal muscles. Triple-seronegative MG (tSN-MG, without detectable AChR, MuSK and LRP4 antibodies), which accounts for ~10% of MG patients, presents a serious gap in MG diagnosis and complicates differential diagnosis of similar disorders. Several AChR antibody positive patients (AChR-MG) also have antibodies against titin, usually detected by ELISA. We have developed a very sensitive radioimmunoprecipitation assay (RIPA) for titin antibodies, by which many previously negative samples were found positive, including several from tSN-MG patients. The validity of the RIPA results was confirmed by western blots. Using this RIPA we screened 667 MG sera from 13 countries; as expected, AChR-MG patients had the highest frequency of titin antibodies (40.9%), while MuSK-MG and LRP4-MG patients were positive in 14.6% and 16.4% respectively. Most importantly, 13.4% (50/372) of the tSN-MG patients were also titin antibody positive. None of the 121 healthy controls or the 90 myopathy patients, and only 3.6% (7/193) of other neurological disease patients were positive. We thus propose that the present titin antibody RIPA is a useful tool for serological MG diagnosis of tSN patients., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Seronegative myasthenia gravis (MG) presents a serious gap in MG diagnosis and understanding. We applied a cell based assay (CBA) for the detection of muscle specific kinase (MuSK) antibodies undetectable by radioimmunoassay. We tested 633 triple-seronegative MG patients' sera from 13 countries, detecting 13% as positive. MuSK antibodies were found, at significantly lower frequencies, in 1.9% of healthy controls and 5.1% of other neuroimmune disease patients, including multiple sclerosis and neuromyelitis optica. The clinical data of the newly diagnosed MuSK-MG patients are presented. 27% of ocular seronegative patients were MuSK antibody positive. Moreover, 23% had thymic hyperplasia suggesting that thymic abnormalities are more common than believed., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To identify novel genetic loci that predispose to early-onset myasthenia gravis (EOMG) applying a two-stage association study, exploration, and replication strategy., Methods: Thirty-four loci and one confirmation loci, human leukocyte antigen (HLA)-DRA, were selected as candidate genes by team members of groups involved in different research aspects of MG. In the exploration step, these candidate genes were genotyped in 384 EOMG and 384 matched controls and significant difference in allele frequency were found in eight genes. In the replication step, eight candidate genes and one confirmation loci were genotyped in 1177 EOMG patients and 814 controls, from nine European centres., Results: ALLELE FREQUENCY DIFFERENCES WERE FOUND IN FOUR NOVEL LOCI: CD86, AKAP12, VAV1, B-cell activating factor (BAFF), and tumor necrosis factor-alpha (TNF-α), and these differences were consistent in all nine cohorts. Haplotype trend test supported the differences in allele frequencies between cases and controls. In addition, allele frequency difference in female versus male patients at HLA-DRA and TNF-α loci were observed., Interpretation: The genetic associations to EOMG outside the HLA complex are novel and of interest as VAV1 is a key signal transducer essential for T- and B-cell activation, and BAFF is a cytokine that plays important roles in the proliferation and differentiation of B-cells. Moreover, we noted striking epistasis between the predisposing VAV1 and BAFF haplotypes; they conferred a greater risk in combination than alone. These, and CD86, share the same signaling pathway, namely nuclear factor-kappaB (NFκB), thus implicating dysregulation of proinflammatory signaling in predisposition to EOMG.

Introduction: Cerebral venous thrombosis (CVT) is an infrequent process in systemic lupus erythematosus. We report the case of a female patient whose initial manifestation of lupus was a CVT., Case Report: A 30-year-old female who presented headaches and diminished visual acuity; on exploring the patient bilateral papilloedema was found. Magnetic resonance imaging revealed the presence of a venous thrombosis in the superior and transversal longitudinal sinus. Complementary explorations showed high levels of antinuclear antibodies with leukopenia and proteinuria. Antiphospholipid antibodies were negative. Following treatment with anticoagulants, the patient's condition improved both clinically and radiologically. Months later a biopsy was performed and revealed a grade IV diffuse glomerulonephritis., Conclusions: In systemic lupus erythematosus, phenomena such as CVT can be the initial form of presentation of the disease. The presence of antiphospholipid antibodies plays a partial role in CVT; other phenomena, such as inflammatory processes, should also be taken into account.