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.

Practical recommendations for the clinical evaluation of patients with hereditary ataxia and hereditary spastic paraplegia.

Hereditary ataxia (HA) and hereditary spastic paraplegia (HSP) are rare diseases; as such, they are rarely managed in general neurology consultations. We present a set of brief, practical recommendations for the diagnosis and management of these patients, as well as a standardised procedure for comprehensive evaluation of disability. We provide definitions for HA and "HA plus," and "pure" and "complicated" HSP; describe the clinical assessment of these patients, indicating the main complementary tests and clinical scales for physical and psychological assessment of the patients; and summarise the available treatments. These recommendations are intended to facilitate daily neurological practice and to unify clinical criteria and disability assessment protocols for patients with HA and HSP.

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.

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

Introducción: Las ataxias (AT) y paraparesias espásticas hereditarias (PEH) son síndromes neu-rodegenerativos raros. Nos proponemos conocer la prevalencia de las AT y PEH en Espa˜na en2019.Pacientes y métodos: Estudio transversal, multicéntrico, descriptivo y retrospectivo de lospacientes con AT y PEH, desde marzo de 2018 a diciembre de 2019 en toda Espa˜na.Resultados: Se obtuvo información de 1933 pacientes procedentes de 11 Comunidades Autóno-mas, de 47 neurólogos o genetistas. Edad media: 53,64 a˜nos ± 20,51 desviación estándar (DE);938 varones (48,5%), 995 mujeres (51,5%). En 920 pacientes (47,6%) no se conoce el defectogenético. Por patologías, 1.371 pacientes (70,9%) diagnosticados de AT, 562 diagnosticados dePEH (29,1%). La prevalencia estimada de AT es 5,48/100.000 habitantes, y la de PEH es 2,24casos/100.000 habitantes. La AT dominante más frecuente es la SCA3. La AT recesiva más fre-cuente es la ataxia de Friedreich (FRDA). La PEH dominante más frecuente es la SPG4, y la PEHrecesiva más frecuente es la SPG7.Conclusiones: La prevalencia estimada de AT y PEH en nuestra serie es de 7,73 casos/100.000habitantes. Estas frecuencias son similares a las del resto del mundo. En el 47,6% no se haconseguido un diagnóstico genético. A pesar de las limitaciones, este estudio puede contribuira estimar los recursos, visibilizar estas enfermedades, detectar las mutaciones más frecuentespara hacer los screenings por comunidades, y favorecer los ensayos clínicos.(AU)

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, descrip-tive study of patients with ataxia and hereditary spastic paraplegia in Spain between March2018 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 wasunidentified 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 paraplegiawere estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequenttype of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia wasFriedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in oursample was SPG4, and the most frequent recessive type was SPG7.Conclusions: In our sample, the estimated prevalence of ataxia and hereditary spastic para-plegia was 7.73 cases per 100 000 population. This rate is similar to those reported for othercountries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, ourstudy provides useful data for estimating the necessary healthcare resources for these patients,raising awareness of these diseases, determining the most frequent causal mutations for localscreening programmes, and promoting the development of clinical trials.(AU)

[Cerebrovascular disease in a tertiary care hospital. The current situation and points to be improved]. / Patología cerebrovascular en un hospital terciario. Situación actual y puntos de mejora.

INTRODUCTION: Caring for patients suffering from a cerebrovascular diseases requires a large quantity of resources which must be optimised. The aim of this study is to analyse the management of stroke in a tertiary care hospital. PATIENTS AND METHODS: All admissions with a diagnosis of stroke were analysed retrospectively for the year 2003. Length of stay, computed tomography in the Emergency Room, origin, previous admissions during the last year, presence of vascular risk factors, stroke subtype, complications and mortality during admission and destination when discharged from hospital, were all recorded. RESULTS: 936 patients were admitted to hospital with a diagnosis of stroke. 80.22% corresponded to acute ischaemic strokes (27.14% lacunar, 18.57% transient ischaemic attacks, 10.25% cardioembolic, 15.44% aterothrombotic, 8.44% infarct of undetermined cause, 0.24% unusual aetiology) and 19.78% corresponded to haemorrhagic strokes (13.99% intraparenchymatous hemorrhage, 5.79% subarachnoid hemorrhage). Intra-hospital mortality was 5.3%. 11% suffered from complications while in hospital, and average length of stay was 10.4 days, being much longer for those patients discharged to a medium-long stay centre (17.5 days). Compared to other series, the incidence of cardioembolic and aterothrombotic subtypes of stroke is low. However, because of the inclusion of neurosurgical patients, an increase of cerebral haemorrhages is observed. CONCLUSIONS: Intra-hospital morbidity and mortality and average length of stay in our series are consistent with those from other centres of similar characteristics. A better coordination with medium-long stay centres along with the presence of neurologists on call, would certainly improve these variables.

[Mitochondrial leukoencephalopathy of infancy: is it an early expression of Leigh syndrome?]. / Leucoencefalopatía mitocondrial del lactante. ¿Forma precoz de un síndrome de Leigh?

INTRODUCTION: Leigh syndrome is probably the most frequent metabolic disorder in infancy and childhood. The classic form of the disease is characterized by bilateral lesions of basal ganglia and brainstem. The extensive involvement of white matter, without radiological basal ganglia abnormalities, is an unusual manifestation of the disease. OBJECTIVE: Four patients who presented the disease during the first year of life are described. PATIENTS AND METHODS: The four patients presented a stereotyped clinical picture, consisting of regression of already acquired psychomotor abilities and very prominent pyramidal signs. These clinical manifestations and results of neuroimaging studies suggested a primary leukodystrophy. Increased values of lactic and piruvic acids suggested a mitochondrial disorder. Enzymatic studies confirmed a mitochondrial respiratory chain deficiency in two patients, and a pyruvate dehydrogenase complex defect in the remaining two patients. The pathological findings in the latter two sisters were consistent with the characteristic microscopic lesions of Leigh syndrome, but with atypical distribution. CONCLUSION: Diagnosis of Leigh syndrome must be taken into consideration in infants presenting with a leukodystrophic clinical and radiological pattern, despite the lack of basal ganglia involvement.

Post-transplantation HTLV-1 myelopathy in three recipients from a single donor.

OBJECTIVES: This paper reports for the first time three cases of infection by HTLV-I via organ transplantation; all the organs coming from the same asymptomatic infected donor. The need is considered for the implementation of compulsory screenings for HTLV antibodies on organ donors and on blood banks. METHODS: The determination of antibodies for HTLV-I/II on samples of serum and cerebral spinal fluid from the patients and the donor was performed by enzyme immunoassay and western blot. Analysis of proviral DNA was performed by polymerase chain reaction. To detect changes in the sequence of amino acids, the tax gene was sequentiated, amplified, and compared with ATK prototype stocks. Spinal cord magnetic resonance imaging, cerebral spinal fluid, and somatosensory evoked potential studies were carried out in all patients. RESULTS: All three transplanted patients developed a myelopathy within a very short period of time. In all three patients and donor the virus belonged to the Cosmopolitan A subtype. The homology of HTLV-I sequences recovered from the patients and donor was 100% in all four cases. Proviral load was high in all three patients. The factors that certainly contributed to the infection in the first place, and the development of the disease later, were on the one hand the high proviral load and their immunosuppressed condition, and on the other the virus genotype, which proved to be an aggressive variant. However, the analysis of the histocompatibility antigen showed that two of the patients carried an haplotype that has been associated with a lower risk of developing this disease. CONCLUSIONS: It is argued that, although in Spain and other European countries there is not compulsory screening for HTLV antibodies because of the studies that show a low seroprevalence, in view of the cases here reported, and to avoid the serious consequences that such infection has on transplanted patients, compulsory screenings, both on organ donors and on blood banks, should be implemented.

Patología cerebrovascular en un hospital terciario. Situación actual y puntos de mejora / Cerebrovascular disease in a tertiary care hospital current situation and issues to be imporved

Introduction. Caring for patients suffering from a cerebrovascular diseases requires a large quantity of resources which must be optimised. The aim of this study is to analyse the management of stroke in a tertiary care hospital. Patients and methods. All admissions with a diagnosis of stroke were analysed retrospectively for the year 2003. Length of stay, computed tomography in the Emergency Room, origin, previous admissions during the last year, presence of vascular risk factors, stroke subtype, complications and mortality during admission and destination when discharged from hospital, were all recorded. Results. 936 patients were admitted to hospital with a diagnosis of stroke. 80,22% corresponded to acute ischaemic strokes (27,14% lacunar, 18,57% transient ischaemic attacks, 10,25% cardioembolic, 15,44% aterothrombotic, 8,44% infarct of undetermined cause, 0,24% unusual aetiology) and 19,78% corresponded to haemorrhagic strokes (13,99% intraparenchymatous hemorrhage, 5,79% subarachnoid hemorrhage). Intra-hospital mortality was 5,3%. 11% suffered from complications while in hospital, and average length of stay was 10,4 days, being much longer for those patients discharged to a medium-long stay centre (17,5 days). Compared to other series, the incidence of cardioembolic and aterothrombotic subtypes of stroke is low. However, because of the inclusion of neurosurgical patients, an increase of cerebral haemorrhages is observed. Conclusions. Intra-hospital morbidity and mortality and average length of stay in our series are consistent with those from other centres of similar characteristics. A better coordination with medium-long stay centres along with the presence of neurologists on call, would certainly improve these variables (AU)

Introducción. La atención a los pacientes con enfermedad cerebrovascular consume gran cantidad de recursos que se necesitan usar óptimamente. El objetivo del presente estudio es analizar la situación de la atención a los ictus en un hospital terciario. Pacientes y métodos. Se analizaron retrospectivamente todos los ingresos con diagnóstico de ictus durante el año 2003. Se registraron la duración de la estancia, la realización de tomografía axial computarizada en Urgencias, procedencia, ingresos previos en el último año, presencia de factores de riesgo vascular, subtipo de ictus, complicaciones y mortalidad durante el ingreso y destino al alta. Resultados. Ingresaron un total de 936 pacientes con diagnóstico de ictus. El 80,22% correspondían a ictus isquémicos (27,14% lacunares, 18,57% accidente isquémico transitorio, 10,25% cardioembólicos, 15,44% aterotrombóticos, 8,44% clasificación incierta, 0,24% causa inhabitual) y el 19,78% a formas hemorrágicas (13,99% hematomas, 5,79% hemorragia subaracnoidea). La mortalidad intrahospitalaria fue del 5,3%, el 11% presentaron algún tipo de complicación durante el ingreso y la estancia media fue de 10,4 días, muy superior en aquellos pacientes con destino al alta a un centro de media-larga estancia (17,5 días). Por subtipo de ictus se aprecia una menor incidencia de ictus cardioembólicos y aterotrombóticos que en otras series. Al incluir pacientes neuroquirúrgicos hay, en cambio, un aumento de hemorragias cerebrales. Conclusiones. La morbimortalidad intrahospitalaria y la estancia media de nuestra serie son acordes a las de los centros de similares características. La mejor coordinación con centros de media-larga estancia junto con la presencia de neurólogos de guardia y/o la creación de unidades de ictus, sin duda, podrían mejorar estos resultados (AU)

Leucoencefalopatía mitocondrial del lactante. ¿Forma precoz de un síndrome de Leigh? / Mitochondrial leukoencephalopathy of infancy: is it an early expression of Leigh syndrome?

Introducción: La enfermedad de Leigh es, probablemente, la enfermedad metabólica más frecuente de presentación en la infancia. La forma clásica de la enfermedad afecta de forma principal a los ganglios basales y el troncoencéfalo. La afectación extensa de la sustancia blanca en ausencia de alteraciones de los ganglios basales es una manifestación poco habitual. Objetivo: Describir el caso de cuatro pacientes que debutaron antes del año de edad. Pacientes y métodos: Los cuatro pacientes presentaron una clínica estereotipada, consistente en regresión de las habilidades psicomotrices adquiridas y desarrollo progresivo de un síndrome piramidal. Las manifestaciones clínicas junto con el hallazgo en la neuroimagen sugerían, inicialmente, una leucodistrofia primaria. La determinación de cifras elevadas de ácido láctico y pirúvico orientaron hacia una enfermedad mitocondrial. Los estudios enzimáticos confirmaron un déficit de los complejos enzimáticos de la cadena respiratoria en dos de los pacientes y, en otras dos hermanas, del complejo piruvato deshidrogenasa. En estas dos últimas, el examen necrópsico mostró las lesiones elementales de la enfermedad de Leigh pero con una distribución inusual. Conclusión: Se debe tener en cuenta que el síndrome de Leigh puede manifestarse con la apariencia de una leucodistrofia en ausencia de las alteraciones típicas de los ganglios basales si afecta a un niño de pocos meses de edad (AU)