Caracterización clínico-cognitiva de la ataxia espinocerebelosa tipo 2 / Clinical-cognitive Characterization of Spinocerebellar Ataxia Type 2

RESUMEN Fundamento: la ataxia espinocerebelosa tipo 2 es una enfermedad genética con un patrón de herencia autosómico dominante. Constituye un problema de salud para Cuba, especialmente para la provincia Holguín, que concentra la población enferma y en riesgo más grande que se haya reportado a nivel mundial hasta el momento. Objetivo: caracterizar desde el punto de vista clínico y cognitivo a pacientes con ataxia espinocerebelosa tipo 2 diagnosticados durante los años 2018 y 2019. Métodos: se realizó un estudio retrospectivo a 28 pacientes con ataxia espinocerebelosa tipo 2 diagnosticados en la Clínica para la Investigación y Rehabilitación de las Ataxias Hereditarias de Holguín que permitieron además correlacionarlas en el tiempo. La muestra quedó conformada por 28 pacientes en estadio ligero de la enfermedad a los cuales se les aplicó la Escala para la Evaluación y Calificación de la Ataxia y la Escala de la Evaluación Cognitiva de Montreal para evaluar la progresión de la enfermedad desde el punto de vista clínico y cognitivo respectivamente con un año de diferencia entre los dos muestreos. Resultados: la edad media de los pacientes fue de 50,3 años con ligero predominio del sexo femenino, el tiempo de evolución promedio fue de 9,82 años resultando mayor para el sexo femenino. La edad media de inicio de la enfermedad fue de 39,54 años. Conclusiones: entre las dos evaluaciones existió una progresión de las manifestaciones cerebelosas y se evidenció un deterioro de las funciones cognitivas, dándole por este estudio un importante papel al cerebelo en ambas funciones.

ABSTRACT Background: spinocerebellar ataxia type 2 is a genetic disease with an autosomal dominant inheritance pattern. It constitutes a health problem for Cuba, especially for the Holguín province, which concentrates the largest sick and at-risk population that has been reported worldwide so far. Objective: to characterize from the clinical and cognitive point of view patients with spinocerebellar ataxia type 2 diagnosed during the years 2018 and 2019. Methods: a retrospective study was carried out in 28 patients with type 2 spinocerebellar ataxia diagnosed at the Holguín Clinic for Research and Rehabilitation of Hereditary Ataxias, which also allowed them to be correlated over time. The sample consisted of 28 patients with a mild stage of the disease to which the Scale for the Assessment and Rating of Ataxia and Montreal Cognitive Assessment Scale were applied to evaluate the progression of the disease from the clinical and cognitive point of view, respectively, with a difference of one year between the two samplings. Results: the mean age of the patients was 50.3 years with a slight predominance of the female sex, the average evolution time was 9.82 years, being longer for the female sex. The mean age of the disease start was 39.54 years. Conclusions: between the two evaluations there was a progression of cerebellar manifestations and a deterioration of cognitive functions was evidenced, giving an important role to the cerebellum in both functions by this study.

Ataxia rating scales--psychometric profiles, natural history and their application in clinical trials.

We aimed to perform a comprehensive systematic review of the existing ataxia scales. We described the disorders for which the instruments have been validated and used, the time spent in its application, its validated psychometric properties, and their use in studies of natural history and clinical trials. A search from 1997 onwards was performed in the MEDLINE, LILACS, and Cochrane databases. The web sites ClinicalTrials.gov and Orpha.net were also used to identify the endpoints used in ongoing randomized clinical trials. We identified and described the semiquantitative ataxia scales (ICARS, SARA, MICARS, BARS); semiquantitative ataxia and non-ataxia scales (UMSARS, FARS, NESSCA); a semiquantitative non-ataxia scale (INAS); quantitative ataxia scales (CATSYS 2000, AFCS, CCFS and CCFSw, and SCAFI); and the self-performed ataxia scale (FAIS). SARA and ICARS were the best studied and validated so far, and their reliability sustain their use. Ataxia and non-ataxia scores will probably provide a better view of the overall disability in long-term trials and studies of natural history. Up to now, no clear advantage has been disclosed for any of them; however, we recommend the use of specific measurements of gait since gait ataxia is the first significant manifestation in the majority of ataxia disorders and comment on the best scales to be used in specific ataxia forms. Quantitative ataxia scales will be needed to speed up evidence from phase II clinical trials, from trials focused on the early phase of diseases, and for secondary endpoints in phase III trials. Finally, it is worth remembering that estimation of the actual minimal clinically relevant difference is still lacking; this, together with changes in quality of life, will probably be the main endpoints to measure in future therapeutic studies.

Ethical dilemmas in genetic testing: examples from the Cuban program for predictive diagnosis of hereditary ataxias.

Predictive testing protocols are intended to help patients affected with hereditary conditions understand their condition and make informed reproductive choices. However, predictive protocols may expose clinicians and patients to ethical dilemmas that interfere with genetic counseling and the decision making process. This paper describes ethical dilemmas in a series of five cases involving predictive testing for hereditary ataxias in Cuba. The examples herein present evidence of the deeply controversial situations faced by both individuals at risk and professionals in charge of these predictive studies, suggesting a need for expanded guidelines to address such complexities.