Neuropsicologia da doença Huntington : fatores preditivos em familiares geneticamente positivos e assintomaticos
Walmir Galvão de Almeida Passos
TESE
Português
T/UNICAMP P268n
Campinas, SP : [s.n.], 1998.
328f.
Orientador: Jayme Antunes Maciel Jr
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Resumo: A Doença de Huntington é uma patologia neurodegenerativa, autossômica dominante, caracterizada por distúrbio do movimento, transtornos psiquiátricos e demência. A doença evoluí de forma insidiosa, e as alterações neuropsicológicas podem anteceder em até 10 anos o início clínico. Desta forma,...
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Resumo: A Doença de Huntington é uma patologia neurodegenerativa, autossômica dominante, caracterizada por distúrbio do movimento, transtornos psiquiátricos e demência. A doença evoluí de forma insidiosa, e as alterações neuropsicológicas podem anteceder em até 10 anos o início clínico. Desta forma, a detecção de alterações neuropsicológicas deveria permitir a separação dos indivíduos assintomáticos em geneticamente positivos e negativos. Este é o objetivo deste trabalho. Uma amostra de 360 indivíduos, provenientes de 57 famílias, foi selecionada para a realização deste trabalho, embora apenas 218 indivíduos tenham se tornado casos válidos. Estes.estão divididos em 125 mulheres e 93 homens. O grupo feminino é discretamente mais jovem, enquanto o grupo masculino apresenta escolaridade mais baixa. Todos os 218 indivíduos foram submetidos ao protocolo de avaliação de demência subcortical e teste de DNA. Entretanto, nem todos puderam realizar Tomografia computadorizada de crânio, Cintilografia de perfusão cerebral, Potencial evocado e E.E.G. O exame neuropsicológico e o exame genético foram realizados pelo método de duplo cego. Os indivíduos deste estudo foram divididos em 3 grupos segundo o tempo de escolaridade (O a 7 anos; 8 a 14 anos; 15 ou + anos de escolaridade). Cada um destes grupos foi subdividido segundo o desempenho no protocolo de avaliação neuropsicológica e o resultado do exame de DNA (+ sintomático, + assintomático e - assintomático).
Os resultados mostram que, exceto no teste de Bender, cuja influência educacional é irrelevante, os demais testes do protocolo não permitem separar os assintomáticos positivos (PA) dos assintomáticos negativos (NE) no grupo de O a 7 anos de escolaridade. Por outro lado, o protocolo permite separar os PA dos NE no grupo de 8 a 14 anos de escolaridade, o que não ocorreu no grupo de 15 ou mais anos de escolaridade. O protocolo de avaliação neuropsicológica esteve alterado em 100% dos doentes, o que permite separar claramente sintomáticos de assintomáticos. A escala de depressão revelou que os PA evoluem para a depressão na medida que evoluem para a doença. O único exame capaz de separar PA de NE foi a Cintilografia com perfusão cerebral. O índice bi-caudado possibilitou a separação de sintomáticos e assintomáticos, mas não de PA e NE. O potencial evocado apresentou alterações em um pequeno percentual de doentes bem como em positivos assintomáticos, mas não permite separar sintomáticos de assintomáticos nem PA dos NE. Concluímos que as alterações neuropsicológicas na fase assintomática permitem separar os geneticamente positivos dos geneticamente negativos na faixa de 8 a 14 anos de escolaridade, e que o teste de Bender, por sofrer quase nenhuma influência educacional, poderia ser escolhido como uma boa opção na avaliação dos positivos assintomáticos Ver menos
Os resultados mostram que, exceto no teste de Bender, cuja influência educacional é irrelevante, os demais testes do protocolo não permitem separar os assintomáticos positivos (PA) dos assintomáticos negativos (NE) no grupo de O a 7 anos de escolaridade. Por outro lado, o protocolo permite separar os PA dos NE no grupo de 8 a 14 anos de escolaridade, o que não ocorreu no grupo de 15 ou mais anos de escolaridade. O protocolo de avaliação neuropsicológica esteve alterado em 100% dos doentes, o que permite separar claramente sintomáticos de assintomáticos. A escala de depressão revelou que os PA evoluem para a depressão na medida que evoluem para a doença. O único exame capaz de separar PA de NE foi a Cintilografia com perfusão cerebral. O índice bi-caudado possibilitou a separação de sintomáticos e assintomáticos, mas não de PA e NE. O potencial evocado apresentou alterações em um pequeno percentual de doentes bem como em positivos assintomáticos, mas não permite separar sintomáticos de assintomáticos nem PA dos NE. Concluímos que as alterações neuropsicológicas na fase assintomática permitem separar os geneticamente positivos dos geneticamente negativos na faixa de 8 a 14 anos de escolaridade, e que o teste de Bender, por sofrer quase nenhuma influência educacional, poderia ser escolhido como uma boa opção na avaliação dos positivos assintomáticos Ver menos
Abstract: Huntington's disease (HD) is an inherited neurodegenerative disorder of midlife onset that produces characteristic, progressive abnormal movements, dementia, and psychiatric and personality abnormalities. The gene responsible of the HD is localized in the short arm of chromosome 4. In...
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Abstract: Huntington's disease (HD) is an inherited neurodegenerative disorder of midlife onset that produces characteristic, progressive abnormal movements, dementia, and psychiatric and personality abnormalities. The gene responsible of the HD is localized in the short arm of chromosome 4. In early 1993 the search for the genetic defect ended with the discovery that the mutation causing Huntington's disease is an expanded, unstable stretch of DNA with a repeating pattern of three nucleotide bases, CAG, located within a previously unknown gene (IT15). The gen's discovering. brought new insights over old questions. It has been long the quest for the existence of neuropsychological patterns as presyntomatic marks of Huntington's disease. The present work aims at contributing to the solution of such a problem. A sample of 360 individuais was selected. They descended from 57 different families. Out of that sample, only 218 participants stayed until the end of our research. Those 218 individuais were. divided into 125 women withan average age of 32, and 93 men with an average age of 34.2. As far as education levei is concerned women had a higher levei of education than men, as stated below: women - 44% of women were in elementary school - 35.2% were in high school - 20.8% were in college men - 5.37% of men were iIIiterate r- 61.75% were in elementary school - 30.09% were in high school -7.52% were in college ali patients were submitted to neuropsichological assessment, but not ali patients were submitted to a depression scale, computadorized tomography (CT), E.E.G, evoked potential, SPECT, and molecular genetic studies.
The molecular genetic test was performed in blind to the results of the neuropsychological assessment. Only afier neuropsychologycal results were separated through cluster analysis in natural group, the results of genetic analyses were added. These data allowed the construction of 3 groups, taking into consideration clinical patterns and the levei of education, as fellows: the (1) the group of symptomatic genetically positive(SP), (2) the group of asymptomatic genetically positive(AP), and (3) the group of asymptomatic genetically negative (NE). The application of MOl1tgomery-Asberg scale revealed that the suggestive signs and symptons of depression (SSD), varing from 7 to 20 points, were more commom among the asyntomatic (both positives and negatives). Actually, we observed an inversion between symptomatic and asymptomatic with SSD and depression. Although the SSD did not allow to separate the asymptomatic (both positive and negative), we can conclude that the asymptomatic negative individual will evolve to heal in great percentage, whereas the SSD of the asymptomatic positive individual will evolve to depression as long as the asymptomatic evolve to disease. These results come in favour of organicity, and explains the confusion between reactive depression and endogenous depression. The exams revealed that the bicaudate ra.-tio (CC/ OT) - obtained by CT of brain - presented a higher sensibility than the other rata to separate the symptomatic from the asymptomatic, having even detected one asymptomatic genetically positive individual among the group of patients. The SPECT revealed alteration in ali patients, and in 68,18% of asymptomatic genetically positive, demonstrating very useful in the presymptomatic stage. The evoked potential revealed alteration of N2, P2 and P3 in 20% of symptomatic positives. As far as the asymptomatic positives are concerned, there were alteration in 7.69% of P2 and 15,38% in the amplitude of P3. Although not specified, such alterations deserve further investigation. In order to atlend the discriminating power of the neuropsychological test to separate the asymptomatic genetically positive individuais from asymptomatic genetically negative ones, the cluster analysis separated the sample in 3 groups according to the education leveI. Each test, divided according to education levei, was subdivided into subgroups with good, average and bad performances. Excepting the abstraction test, the group of 1 through 7 years of school allowed separating symptomatic from the asymptomatic, but they could not separate the asymptomatic positives from the asymptomatic negatives. The visuospatial praxis and mental set was the only one capable of separating the asymptomatic genetically positives from the asymptomatic genetically negatives at the levei of 1 through 7 years of school, and 8 through 14 years of school. For the other tests - such as atlention, memory, abstraction, visuospatial praxis and mental set - only the levei from 8 through 14 years of school allowed separating the asymptomatic genetically. positives from the asymptomatic genetically negatives. Excepted the atlention test, the group of 15 years of school and above allowed separating the symptomatic from asymptomatic, and could not separate the asymptomatics positives from the asymptomatic negatives Ver menos
The molecular genetic test was performed in blind to the results of the neuropsychological assessment. Only afier neuropsychologycal results were separated through cluster analysis in natural group, the results of genetic analyses were added. These data allowed the construction of 3 groups, taking into consideration clinical patterns and the levei of education, as fellows: the (1) the group of symptomatic genetically positive(SP), (2) the group of asymptomatic genetically positive(AP), and (3) the group of asymptomatic genetically negative (NE). The application of MOl1tgomery-Asberg scale revealed that the suggestive signs and symptons of depression (SSD), varing from 7 to 20 points, were more commom among the asyntomatic (both positives and negatives). Actually, we observed an inversion between symptomatic and asymptomatic with SSD and depression. Although the SSD did not allow to separate the asymptomatic (both positive and negative), we can conclude that the asymptomatic negative individual will evolve to heal in great percentage, whereas the SSD of the asymptomatic positive individual will evolve to depression as long as the asymptomatic evolve to disease. These results come in favour of organicity, and explains the confusion between reactive depression and endogenous depression. The exams revealed that the bicaudate ra.-tio (CC/ OT) - obtained by CT of brain - presented a higher sensibility than the other rata to separate the symptomatic from the asymptomatic, having even detected one asymptomatic genetically positive individual among the group of patients. The SPECT revealed alteration in ali patients, and in 68,18% of asymptomatic genetically positive, demonstrating very useful in the presymptomatic stage. The evoked potential revealed alteration of N2, P2 and P3 in 20% of symptomatic positives. As far as the asymptomatic positives are concerned, there were alteration in 7.69% of P2 and 15,38% in the amplitude of P3. Although not specified, such alterations deserve further investigation. In order to atlend the discriminating power of the neuropsychological test to separate the asymptomatic genetically positive individuais from asymptomatic genetically negative ones, the cluster analysis separated the sample in 3 groups according to the education leveI. Each test, divided according to education levei, was subdivided into subgroups with good, average and bad performances. Excepting the abstraction test, the group of 1 through 7 years of school allowed separating symptomatic from the asymptomatic, but they could not separate the asymptomatic positives from the asymptomatic negatives. The visuospatial praxis and mental set was the only one capable of separating the asymptomatic genetically positives from the asymptomatic genetically negatives at the levei of 1 through 7 years of school, and 8 through 14 years of school. For the other tests - such as atlention, memory, abstraction, visuospatial praxis and mental set - only the levei from 8 through 14 years of school allowed separating the asymptomatic genetically. positives from the asymptomatic genetically negatives. Excepted the atlention test, the group of 15 years of school and above allowed separating the symptomatic from asymptomatic, and could not separate the asymptomatics positives from the asymptomatic negatives Ver menos
Neuropsicologia da doença Huntington : fatores preditivos em familiares geneticamente positivos e assintomaticos
Walmir Galvão de Almeida Passos
Neuropsicologia da doença Huntington : fatores preditivos em familiares geneticamente positivos e assintomaticos
Walmir Galvão de Almeida Passos
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