Paula Coutinho's outstanding contribution to the definition of Machado-Joseph disease / A excepcional contribuição de Paula Coutinho na definição da doença de Machado-Joseph

ABSTRACT Machado-Joseph disease, also known as spinocerebellar ataxia type 3, is the most common form of autosomal dominant ataxia in the world. Paula Coutinho, a highly-regarded Portuguese neurologist worldwide, had a seminal participation in the definition of this disease, more than 40 years ago.

RESUMO A doença de Machado-Joseph, também conhecida como ataxia espinocerebelar tipo 3 (SCA3), representa a forma mais comum de ataxia hereditária autossômica dominante no mundo. Paula Coutinho, neurologista portuguesa de reputação mundial, teve participação fundamental na definição desta doença há mais de 40 anos.

Risk perception in subjects at-risk for Familial Amyloidotic Polyneuropathy / Percepción del riesgo en sujetos con riesgo de Polineuropatía Amiloide Familiar

Abstract The aims of this study are to know if subjects at-risk were aware of their 50% risk for Familial Amyloidotic Polyneuropathy (FAP); to know the value of the subjective risk; to understand the association between sociodemographic characteristics and risk perception, and between the risk status and the subjective perception of risk. 174 subjects 50% at-risk for FAP were tested. 52.9% subjects at-risk were aware of their 50% risk condition. The mean value of the subjective risk was higher and closer to 50% when the subjects were aware of their 50% risk condition. Education was associated to a higher awareness of being at 50% risk. It seems that information on previous knowledge before performing the genetic counselling increases the subjective risk.

Resumen Los objetivos de este estudio son saber si los sujetos en riesgo eran conscientes de su riesgo del 50% para la polineuropatía amiloide familiar (PAF); conocer el valor del riesgo subjetivo; y comprender la asociación entre las características sociodemográficas y la percepción del riesgo y entre el riesgo real y la percepción subjetiva del riesgo. Se examinaron 174 sujetos con riesgo de PAF del 50%. 52,9% de los sujetos en riesgo eran conscientes de su condición de riesgo del 50%. El valor medio del riesgo subjetivo fue mayor y más cercano al 50% cuando los sujetos eran conscientes de su condición de riesgo del 50%. La educación se asoció a una mayor conciencia de estar al 50% de riesgo. Parece que la información sobre los conocimientos previos antes de realizar el asesoramiento genético aumenta el riesgo subjetivo.

Motivation to perform presymptomatic testing in portuguese subjects at-risk for late-onset genetic diseases

El papel del psicólogo clínico en el contexto del consejo genético incluye brindar apoyo a los sujetos en riesgo en el proceso de toma de decisiones, independientemente de la decisión adoptada por el sujeto (conociendo o no el resultado de las pruebas genéticas). El estudio que se informa aborda la motivación para realizar las pruebas pre-sintomáticas (PPS) de sujetos en situación de riesgo para tres enfermedades: polineuropatía amiloide familiar (PAF), la enfermedad de Huntington (EH) y la enfermedad de Machado-Joseph (EMJ) y comparar con la motivación para realizar las PPS para hemocromatosis (HH). La muestra consistió en 213 sujetos portugueses que tenían riesgo genético para contraer las tres enfermedades y 31 sujetos en situación de riesgo genético para contraer hemocromatosis. Ellos fueron evaluados con una entrevista para obtener datos sociodemográficos y debían responder a una pregunta sobre la motivación para llevar a cabo las pruebas pre-sintomáticas. Se obtuvieron siete categorías principales y las siguientes son las más significativas para PAF, EH y EMJ: razones relacionadas con el futuro, razones relacionadas con los demás y razones relacionadas con la curiosidad y la necesidad de conocer. Para hemocromatosis, las más importantes resultaron ser razones relacionadas con los demás y las relacionadas con las características de la enfermedad. La motivación para realizar el test pre-sintomático (PST) de la PAF, EH y EMJ es externa y sin relación con la enfermedad, mientras que la motivación de los sujetos en situación de riesgo para la HH está relacionada con la enfermedad. Las razones relacionadas con los demás es una motivación común en ambos grupos. A los sujetos también les preocupa la posibilidad de transmitir la enfermedad a sus hijos.

The role of the clinical psychologist in the context of genetic counseling includes support for the process of decision-making for subjects at-risk, regardless of the decision that was made. For this, it is important to know the motivations behind these decisions. What may be considered advant-ageous and justifiable reasons to perform the PST for genetic diseases from the medical and public point of view, i.e., planning for the future, helping in the choice of a profession, family planning, improving quality of life and contributing to health, may not be recognized as such by the individual seeking the PST. This study addresses the motivation to perform the presymptomatic testing (PST) of subjects at-risk for three diseases, Familial Amyloid Polyneuro pathy (FAP), Huntington's disease (HD), and Machado-Joseph disease (MJD), compared with the motivation to perform the PST for Hemochromatosis (HH). FAP, HD and MJD are three genetic (monogenic) autosomal dominant late-onset diseases (LON-Ds) with no cure. FAP is a progressive sensorimotor and autonomic neuropathy of adult hood. HD is characterized by a triad of clinical symptoms of chorea (motor, cognitive and psychiatric symptoms), emotional distress and cognitive decline. MJD is characterized by slowly progressive clumsiness in the arms and legs, a staggering lurching gait, sometimes mistaken for drunkenness, difficulty with speech and swallowing, involuntary eye movements, and may be accompanied by double vision or bulging eyes, and lower limb spasticity. HH is a disease in which too much iron accumulates in parenchymal organs, leading to iron overload and subsequent organ toxicity and failure. The study participants consisted in 213 subjects at genetic risk for FAP, HD, and MJD and 31 subjects at genetic risk for HH, that were assessed through an interview to obtain sociodemographic data and the answer to one question about motivation to perform PST: "Which were the reasons that led you to perform the predictive test? "This study was carried out in Center for Predictive and Preventive Genetics (CGPP), Institute for Molecular and Cell Biology (IBMC), Porto (Portugal). This research used a mixed-method, since qualitative and quantitative techniques of data analysis were used. Before deciding to seek genetic counseling and to know their genetic status, subjects at-risk have naturally considered their motives and it was probably the pro-counseling reasons the ones dictating the motivation to perform the PST. This may suggest that in fact there is a prior self-selection to the test, i.e. only those considering to have emotional skills to go through the process, performing the test. Seven major categories were obtained. The most significant ones for FAP, HD and MJD were reasons related to the future, reasons related to others and reasons related to curiosity and to the need to know. For HH, the most important ones were reasons related to others and reasons related to the characteristics of the disease. The motivation of subjects at-risk to perform the PST for FAP, HD and MJD is external and unrelated to the disease, while the motivation of subjects at-risk to perform the PST for HH is related to the disease. Reasons related to others area common motivation: as subjects at-risk for FAP, HD and MJD, subjects at-risk for HH also chose reasons related to others as one of the most important motivations to carry out the PST. These subjects also care about the fact that they can transmit the disease to their children and care about other family members which are already ill. The category reasons related to others includes sub-categories that identify the person and the situation that led to the decision to perform a PST. Subjects at-risk are also concerned about the fact that they have to decide whether or not to have children and its economic implications.

Depression as the middle-and long-term impact for pre-symptomatic testing of late-onset neurodegenerative disorders / A depressão como indicador do impacto psicológico a médio e longo prazo do teste pré-sintomático de doenças neurodegenerativas de início tardio / La depresión como el indicador de impacto psicológico a la media y largo plazo de la prueba pre-sintomática para enfermedades de aparición tardía

This cross-sectional study investigated depression as the middle- (4 years) and long-term (7 and 10 years) psychological impact of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset diseases: Huntington's disease (HD), Machado-Joseph disease (MJD) and familial amyloidotic polyneuropathy (FAP) TTR V30M. It included 203 subjects: 170 (83.7%) underwent the PST for FAP, 29 (14.3%) for HD and 4 (2%) for MJD. Of these 203, 73 were still asymptomatic carriers, 29 (14.5%) were symptomatic, 9 (4.5%) were FAP liver transplanted patients and 89 (44.5%) were non-carriers. Subjects were mainly women (58.1%) and married (66.5%). The Beck Depression Inventory (BDI) was used to evaluate depression. Scores were higher for symptomatic carriers and for those who have made one or more psychological support consultations over the years. For the formers, the mean scores pointed to mild depression. Asymptomatic carriers and non-carriers had similar scores but it was impossible to differentiate the psychological impact between the medium and long-term. For symptomatic carriers, there were significant differences between the middle- and long-term. The study indicates that depression occurs only when subjects had previously manifested the first symptoms of their neurologic disease.

Este estudo transversal investigou a depressão como indicador do impacto psicológico do teste pré-sintomático (TPS) a médio (quatro anos) e longo prazo (de 7 a 10 anos) de doenças neurológicas de início tardio: a doença de Huntington (DH), doença de Machado-Joseph (DMJ) e polineuropatia amiloidótica familiar PAF (TTR V30M). 203 sujeitos participaram no estudo: 170 (83,7%) submetidos ao TPS para PAF, 29 (14,3%) para o DH e 4 (2%) para DMJ. Destes 203, 73 eram portadores assintomáticos, 29 (14,5%) já eram sintomáticos, 9 (4,5%) pacientes com PAF, já tinham realizado o transplante hepático e 89 (44,5%) eram não-portadores. A amostra era constituída maioritariamente por mulheres (58,1%) e por sujeitos casados (66,5%). Utilizou-se o Inventário da Depressão de Beck (BDI). Os scores mais elevados foram observados nos portadores sintomáticos e nos sujeitos que tinham realizado consultas de psicologia com scores indicadores de depressão leve. Os portadores assintomáticos e os não-portadores apresentaram médias semelhantes. Para os portadores sintomáticos, encontrámos diferenças significativas entre o médio e o longo prazo. Este estudo conclui que a depressão pode ocorrer nos indivíduos que já manifestam os primeiros sintomas da respectiva doença neurológica.

Este estudio transversal investigó la depresión a la media (4 años) y largo plazo (7 y 10 años) del impacto psicológico de la prueba pre-sintomática (PPS) para 3 enfermedades autosómicos, dominantes, de aparición tardía: la enfermedad de Huntington (EH), la enfermedad de Machado-Joseph (EMJ) y la polineuropatia amiloide familiare (PAF) o polineuropatia amiloide da transtiretina FAP (TTR V30M). Participaron 203 sujetos: 170 (83,7%) para PPS para PAF, 29 (14,3%) para EH y 4 (2%) para EMJ. De estos 203, 73 estaban todavía portador asintomático, 29 (14,5%) eran sintomáticos, 9 (4,5%) fueron PAF pacientes con trasplante hepático y 89 (44,5%) eran no-portadores. Eran en su mayoría mujeres (58,1%) y casados (66,5%). Se utilizó el Inventario de Depresión de Beck (IDB). Los puntajes fueron mayores para las portadoras sintomáticas y para aquellos que han hecho consultas de apoyo psicológico con puntuaciones medias de depresión leve. Los portadores asintomáticos y no portadores tuvieron puntajes similares. Para portadores sintomáticos, hubo diferencias significativas entre el medio y largo plazo. Este estudio concluye que la depresión puede ocurrir en personas que ya muestran los primeros síntomas de la enfermedad neurológica.

Mid- and long-term anxiety levels associated with presymptomatic testing of Huntington's Disease, Machado-Joseph Disease, Machado-Joseph disease, and familial amyloid polyneuropathy

Objective: To study anxiety as a variable of the mid- and long-term psychological impact of pre-symptomatic testing for three autosomal dominant late-onset disorders – Huntington’s disease (HD), Machado-Joseph disease (MJD) and familial amyloid polyneuropathy (FAP) TTR V30M – in a Portuguese sample. Methods: This cross-sectional study included 203 participants: 170 (83.7%) underwent pre-symptomatic testing for FAP, 29 (14.3%) for HD, and 4 (2%) for MJD. Of the 203 participants, 73 (36.0%) were asymptomatic carriers, 29 (14.5%) were symptomatic carriers, 9 (4.5%) were diagnosed with FAP and had a liver transplant, and 89 (44.5%) were non-carriers. Most were women (58.1%) and married (66.5%). The anxiety variable was assessed using the Zung Self-Rating Anxiety Scale (SAS). Results: The anxiety scores were higher for symptomatic carriers and for those who underwent psychological support consultations over the years. For symptomatic carriers, the mean scores were superior to 40 points, which reflects clinical anxiety. Conclusion: Although it was not possible to differentiate between the mid- and long-term psychological impacts, this study supports the conclusion that the proximity to the age of symptoms onset might be a trigger for anxiety.