Epidemiology of ataxia and hereditary spastic paraplegia in Spain: A cross-sectional study.

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.

Epidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study. / Mapa epidemiológico transversal de las ataxias y paraparesias espásticas hereditarias en España.

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.

Titin antibodies in "seronegative" myasthenia gravis--A new role for an old antigen.

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.

MuSK autoantibodies in myasthenia gravis detected by cell based assay--A multinational study.

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.

[Cerebral venous thrombosis as the presenting symptom of systemic lupus erythematosus]. / Trombosis venosa cerebral como presentación de lupus eritematoso sistémico.

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.

Trombosis venosa cerebral como presentación de lupus eritematoso sistémico / Cerebral venous thrombosis as the presenting symptom of systemic lupus erythematosus

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 (AU)

Introducción. La trombosis venosa cerebral (TVC) no es un proceso habitual en el lupus eritematosos sistémico. Presentamos una paciente cuya manifestación inicial del lupus fue una TVC. Caso clínico. Paciente de 30 años de edad que presenta cefalea y disminución de la agudeza visual; en la exploración destaca un papiledema bilateral. La resonancia magnética realizada demuestra la presencia de una trombosis venosa en el seno longitudinal superior y transverso. Las exploraciones complementarias mostraron altas concentraciones de anticuerpos antinucleares con leucopenia y proteinuria. Los anticuerpos antifosfolípidos fueron negativos. Tras un tratamiento anticoagulante, mejoró clínica y radiológicamente. Meses más tarde se realizó una biopsia, que demostró una glomerulonefritis difusa grado IV. Conclusión. En el lupus eritematoso sistémico, fenómenos como la TVC pueden ser la forma de manifestación inicial de la enfermedad. La presencia de anticuerpos antifosfolípidos participa de forma parcial en la TVC; deberían considerarse otros fenómenos, como los inflamatorios (AU)