Spinocerebellar Ataxia Type 2

1. Introduction: The autosomal dominant cerebellar ataxias (ADCA) are a clinically, pathologically and genetically heterogeneous group of neurodegenerative disorders caused by degeneration of cerebellum and its afferent and efferent connections. The degenerative process may additionally involves the ponto- medullar systems, pyramidal tracts, basal ganglia, cerebral cortex, peripheral nerves (ADCA I) and the retina (ADCA II), or can be limited to the cerebellum (ADCA III) (Harding et al., 1993). The most common of these dominantly inherited autosomal ataxias, ADCA I, includes many Spinocerebellar Ataxias (SCA) subtypes, some of which are caused by pathological CAG trinucleotide repeat expansion in the coding region on the mutated gene. Such is the case for SCA1, SCA2, SCA3/MJD, SCA6, SCA7, SCA17 and Dentatorubral-pallidoluysian atrophy (DRPLA) (Matilla et al., 2006). Among the almost 30 SCAs, the variant SCA2 is the second most prevalent subtype worldwide, only surpassed by SCA3 (Schöls et al., 2004; Matilla et al., 2006; Auburger, 2011)..

Eye Movement Abnormalities in Neurodegenerative Diseases

Neurodegenerative disorders consist in heterogeneous group of neurological conditions characterized by a wide spectrum of clinical features resulting from a progressive involvement of distinct neuron populations. Oculomotor abnormalities take a key place in the clinical picture of these disorders because the neurodegenerative processes involve the brain circuits of eye movements. The most common abnormalities include the saccadic dysfunction, fixation instability, and abnormal smooth pursuit. The clinical assessment of oculomotor function can help to differentiate diagnosis, while electrophysiological measures provide useful biomarkers for the understanding of disease physiopathology and progression. In this chapter, we review the state of the art of the eye movement’s deficits in some neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and the hereditary ataxias

Non spontaneous saccadic movements identification in clinical electrooculography using machine learning

In this paper we evaluate the use of the machine learning algorithms Support Vector Machines, K-Nearest Neighbors, CART decision trees and Naive Bayes to identify non spontaneous saccades in clinical electrooculography tests. Our approach tries to solve problems like the use of manually established thresholds present in classical methods like identification by velocity threshold (I-VT) or identification by dispersion threshold (I-DT). We propose a modification to an adaptive threshold estimation algorithm for detecting signal impulses without the need of any user input. Also, a set of features were selected to take advantage of intrinsic characteristics of clinical electrooculography tests. The models were evaluated with signals recorded to subjects affected by Spinocerebellar Ataxia type 2 (SCA2). Results obtained by the algorithm shows accuracies over 97%, recalls over 97% and precisions over 91% for the four models evaluated.Universidad de Málaga, Campus de excelencia de Andalucía Tec

Evaluación de la marcha en pacientes con ataxia espinocerebelosa tipo 2: fundamentos teóricos (Revisión)

The present work presents the results of a bibliographic review carried out on the methods most used for the evaluation of human gait, both normal and pathological. It is particularized in those most used in Cuba, in patients with Type 2 Spinocerebellar Ataxia, specifically in the Holguín province, which has the highest international rate of people with this disease. The study of human gait requires great importance, whose disorder constitutes one of the initial symptoms when the patient begins to debut with ataxia, and its involvement is so progressive that it significantly influences the transition from one stage of the disease to another. The methods for evaluating human gait are varied, and can be grouped into kinematic and kinetic. Some authors refer to tests, scales and indices as methods, when in reality they are measurement instruments that yield quantifiable results. Those of greater application have a qualitative origin, a reason that limits their comparison with the patterns of normal human gait, and to be able to know the level of affectation of each patient, particularized by each indicator that characterizes locomotion. The use of the Mobility Lab stands out as an advanced technology instrument used at the clinical level. This provides quantifiable results, in real time, of most of the indicators that characterize human gait, through the placement of sensors in various parts of the patient's body.En el presente trabajo se exponen los resultados de una revisión bibliográfica realizada sobre los métodos más empleados para la evaluación de la marcha humana, tanto normal como patológica. Se particulariza en aquellos más utilizados en Cuba, específicamente en la provincia de Holguín, en pacientes con ataxia espinocerebelosa tipo 2, ya que esta región presenta la tasa más elevada a nivel internacional de personas con esta enfermedad. El estudio de la marcha humana tiene gran importancia, pues su trastorno se reconoce como uno de los síntomas iniciales de la ataxia y su afectación progresiva resulta un indicador significativo del tránsito de un estadio a otro de la enfermedad. Los métodos para la evaluación de la marcha humana son variados y se pueden agrupar en cinemáticos y cinéticos. Algunos autores también se refieren a test, escalas e índices como métodos, cuando en realidad son instrumentos de medición que arrojan resultados cuantificables. Se destaca el empleo del Mobility Lab, como instrumento de avanzada tecnología que se emplea a nivel clínico y que proporciona resultados cuantificables, en tiempo real, de la mayoría de los indicadores que caracterizan a la marcha humana

Estudio de la atención físico-terapéutica a las alteraciones respiratorias en pacientes con Ataxia Espinocerebelosa tipo 2 (Original)

The investigation tackles the aspects related with the physical therapeutic attention to the respiratory alterations in patients with Spinocerebellar Ataxia type 2, this is an entity neurodegenerative that affects the driving area, cognitive and respiratory fundamentally. Product that limitations that affect the performance of the professionals of Physical Culture that labor in Salad’s areas that they labor with this pathology exist . A system of derivative actions of the results of the diagnostic study for the sake of contributing to the improvement of the respiratory alterations of these patientswas designed. They use methods of theoretic order for it, in investigation (poll, observation) (analytical synthetic, inductive deductive and of the empiric level. The information was submitted to the correspondent statistical processing, which offers the level of reliability and validity to these.La investigación aborda los aspectos relacionados con la atención físico- terapéutica a las alteraciones respiratorias en pacientes con Ataxia Espinocerebelosa tipo 2, esta es una entidad neurodegenerativa que afecta el área motriz, cognitiva y respiratoria fundamentalmente. Producto que existen limitaciones que afectan el desempeño de los profesionales de Cultura física que laboran en las áreas de Salud que laboran con esta patología. Se diseñó un sistema de acciones derivadas de los resultados del estudio diagnóstico, en aras de contribuir al mejoramiento de las alteraciones respiratorias de estos pacientes. Para ello, en la investigación se emplean métodos de orden teórico (analítico-sintético, inductivo-deductivo y del nivel empírico (encuesta, observación). La información fue sometida al correspondiente procesamiento estadístico, lo cual le ofrece el nivel de confiabilidad y validez a estos

Influencia de un programa de ejercicios físicos en la mejora del dolor de pacientes fibromiálgicos

Introduction: Fibromyalgia is a rheumatic disease of unknown etiology that causes skeletal-muscle disability consisting in chronic and diffuse pain. It is characterized by producing limitations in activity and restrictions in participation, decreasing considerably the quality of life of patients, affecting both the biological and psychological areas, where pain is the main symptom. In this context, different treatments are used where therapeutic physical exercise is a viable alternative.Objective: To assess the influence of a physical exercise program for the reduction of pain in fibromyalgia, which includes the orientation to the family as an educational measure.Material and method: A pilot study of quantitative, pre-experimental and exploratory type was carried out. A therapeutic physical intervention was carried out where a program of low-impact aerobics was used (walking, ergometric bicycle, walking in place, walking in the water and musical rhythmic exercises), flexibility, muscle strengthening, joint mobility, throwing fitness ball and Chinese therapeutic gymnastics (Qi-gong).Results and conclusions: It was found that the program of physical exercises correctly dosed and planned is an important tool in pain´s treatment of patients with fibromyalgia, since 100% of the patients significantly improved (p < 0.001) when the pre-test and post-test was compared.Introducción: La fibromialgia es una enfermedad reumática discapacitante consistente en la presencia de dolor crónico de los músculos esqueléticos, disminuyendo considerablemente la calidad de vida de quienes la padecen. Los tratamientos disponibles vas desde el uso de estrategias farmacológicas hasta la terapia, donde el ejercicio físico terapéutico es una alternativa viable. Objetivo: valorar la influencia de un programa de ejercicios físicos para la disminución del dolor en la fibromialgia, que incluye la orientación a la familia como medida educativa. Material y método: se realizó un estudio piloto de tipo cuantitativo, prospectivo, longitudinal y comparativo. Se efectuó una intervención física terapéutica donde se utilizó un programa de ejercicios aeróbicos de bajo impacto (Caminar, Bicicleta ergométrica, marcha en el lugar, ejercicios de hidrocinesiterapia particularmente el entrenamiento de la marcha y ejercicios de estiramientos, ejercicios rítmicos musicales), de flexibilidad, de fortalecimiento muscular, movilidad articular, de lanzamiento de balón medicinal y gimnasia terapéutica China, específicamente el Qi-gong. Resultados y conclusiones: se encontró que el programa de ejercicios físicos correctamente dosificado y planificado es una herramienta importante en el tratamiento del dolor en pacientes con fibromialgia, ya que el 100% de los pacientes mejoraron significativamente (p<0.001) después de la intervención

Familial Alzheimer's disease-associated presenilin-1 alters cerebellar activity and calcium homeostasis

Familial Alzheimer's disease (FAD) is characterized by autosomal dominant heritability and early disease onset. Mutations in the gene encoding presenilin-1 (PS1) are found in approximately 80% of cases of FAD, with some of these patients presenting cerebellar damage with amyloid plaques and ataxia with unclear pathophysiology. A Colombian kindred carrying the PS1-E280A mutation is the largest known cohort of PS1-FAD patients. Here, we investigated PS1-E280A-associated cerebellar dysfunction and found that it occurs early in PS1-E208A carriers, while cerebellar signs are highly prevalent in patients with dementia. Postmortem analysis of cerebella of PS1-E280A carrier revealed greater Purkinje cell (PC) loss and more abnormal mitochondria compared with controls. In PS1-E280A tissue, ER/mitochondria tethering was impaired, Ca2+ channels IP3Rs and CACNA1A were downregulated, and Ca2+-dependent mitochondrial transport proteins MIRO1 and KIF5C were reduced. Accordingly, expression of PS1-E280A in a neuronal cell line altered ER/mitochondria tethering and transport compared with that in cells expressing wild-type PS1. In a murine model of PS1-FAD, animals exhibited mild ataxia and reduced PC simple spike activity prior to cerebellar β-amyloid deposition. Our data suggest that impaired calcium homeostasis and mitochondrial dysfunction in PS1-FAD PCs reduces their activity and contributes to motor coordination deficits prior to Aβ aggregation and dementia. We propose that PS1-E280A affects both Ca2+ homeostasis and Aβ precursor processing, leading to FAD and neurodegeneration

Motor Decline in Clinically Presymptomatic Spinocerebellar Ataxia Type 2 Gene Carriers

BACKGROUND: Motor deficits are a critical component of the clinical characteristics of patients with spinocerebellar ataxia type 2. However, there is no current information on the preclinical manifestation of those motor deficits in presymptomatic gene carriers. To further understand and characterize the onset of the clinical manifestation in this disease, we tested presymptomatic spinocerebellar ataxia type 2 gene carriers, and volunteers, in a task that evaluates their motor performance and their motor learning capabilities. METHODS AND FINDINGS: 28 presymptomatic spinocerebellar ataxia type 2 gene carriers and an equal number of control volunteers matched for age and gender participated in the study. Both groups were tested in a prism adaptation task known to be sensible to both motor performance and visuomotor learning deficits. Our results clearly show that although motor learning capabilities are intact, motor performance deficits are present even years before the clinical manifestation of the disease start. CONCLUSIONS: The results show a clear deficit in motor performance that can be detected years before the clinical onset of the disease. This motor performance deficit appears before any motor learning or clinical manifestations of the disease. These observations identify the performance coefficient as an objective and quantitative physiological biomarker that could be useful to assess the efficiency of different therapeutic agents