Machado-Joseph disease op azorean ancestry in Brazil: the Catarina kindred neurological, neuroimaging, psychiatric and neuropsychological findings in the largest known family, the «Catarina» kindred

Radvany, J.; Camargo, C.H.P.; Costa, Z.M.; Fonseca, N.C.; Nascimento, E.D.

doi:10.1590/S0004-282X1993000100004

Abstracts

At the moment 9 seemingly independent families with the clinical diagnosis of MJD are known in Brazil. The largest family tree of Azorean ancestry contatins 622 individuals in 9 generations. 236 were examined, 39 found to be affected by two examiners. Pheno-types I, II and III were expressed by 12, 23 and 4 patients with age of onset by phenotypea being 10-48, 14-54 and 30-55 respectively. Although clinically more severe, juvenile onset type I disease did not show as severe a ponto-mesencephialic atrophy on MRI as the father with type II disease of similar symptomatic duration. None of the 8 patients examined with MRI showed olivary atrophy or pallidal abnormalities. 12 affected and 23 at risk were evaluated with neuropsychological tests. Attention was normal in both groups. Verbal memory scores were below normal in the affected and there was greater decay with time than in the risk group. Both scored below normal in identifying silluettes and constructional praxis. Visual memory scores were well below normal for both, with many rotations but no omissions or confabulations. A peculiar pattern of multiplying internal details called «the fly-eye effect» was observed in 6 affected and 8 at risk. Defective color distinction when multiple colors presented close to each other, in face of proper naming of individual colors («color simultantagnosia»), was looked for in 29 people. 4/10 affected and 4/19 at risk showed this phenomenon. Cognitive dysfunctions in this MJD family are prominent in the sphere of vision. Whether they constitute an early manifestation in those at risk and thus serve as a clinical identifier of the illnes is yet to be established. Depression was looked for in the history of the family with DSM III-R criteria and an atempt at quantification with the Montgomery-Asberg Rating Scale. There was no significant quantitative difference between affected and at risk. Once undeniably symptomatic however, the patients had no, or less depression than themselves before or tat the early stages of the illness. Covert depression was appropriately excluded. Fully established MJD in this family seemed to exert a protective effect from depression.

Machado-Joseph disease; MRI; neuropsychology; visual memory; color naming; depression

Há, até o momento, notícia de 9 famílias não aparentadas com o diagnóstico clínico de doença de Machado-Joseph (MJD) no Brasil. Esta é a maior família do mundo com a doença. É de origem açoriana e contém 622 indivíduos na árvore genealógica. Destes, 236 foram examinados. Dois examinadores julgaram 39 como afetados. Respectivamente 12, 23 e 4 pacientes tinham os fenôtipos I, II e III dia doença, com idades no início variando entre 10-48, 14-54 e 30-55. Doença tipo I de início juvenil não mostrou atrofia tão severa nas imagens por ressonância magnética (RM) quanto doença tipo II de duração igual, demonstrando que severidade clínica e grau de atrofia não caminham paralelamente. Nenhum dos 8 pacientes examinados por RM tinha atrofia olivar ou anormalidades no globo pálido. Doze pacientes e 23 sob risco foram submetidos a avaliiação neuropsicológica. A atenção foi normal em todos. Memória verbal estava pior nos doentes com maior decaimento com o tempo que nos sob risco. Ambos os grupos tiveram pontuação abaixo do normal na identificação de silhuetas e praxia construtiva. Memória visual estava bem abaixo do normal para ambos, com muitas rotações, porém sem omissões ou confabulação. Padrão peculiar de multiplicação dos detalhes internos, que denominamos o «efeito olho de mosca» foi visto em 6 doentes e 8 sob risco. Discriminação defeituosa de cores, quando múltiplas cores eram apresentadas liado a lado, na ausência de anomia ou cegueira a cores, caracterizável como «simultamagnosia a cores», surgiu como achado e foi pesquisada em 29 sujeitos. 4/10 doentes e 6/19 sob risco mostraram esta dificuldade. Conclui-se que disfunções cognitivas na esfera visual são proeminentes nesta família. Se seriam próprias da doença e manifestação precoce daqueles sob risco, está ainda para ser estabelecido. Depressão foi avaliada com critérios do DSM III-R e com o Montgomery-Asberg Depression Rating Scale. Não houve diferença entre doentes e sob risco. Entretanto, os pacientes tiveram menos depressão do que tinham tido antes ou nas fases precoces da doençta. A MJD plenamente instalada parecia exercer efeito protetor da depressão.

doença de Machado-Joseph; ressonância magnética; neuropsicologia; memória visual; distinção de cores; depressão

J. Radvany^I; C.H.P. Camargo^II; Z.M. Costa^III; N.C. Fonseca^IV; E.D. Nascimento^V

^IDepartments of Neurology land Neuroimaging, Hospital Israelita Albert Einstein, São Paulo

^IIMD; Neuropsychology Section, Division of Neurosurgery of the Hospital das Clinicas, Faculdade de Medicina da Universidade de São Paulo (HC, FMUSP) BA

^IIISocial Services of the Children's Institute, HC, FMUSP

^IVInstituto de Neurologia e Neurocirurgia, Hospital da Beneficência Portuguesa de São Paulo MD

^VDepartment of Neurology, Hospital Marieta Konder, Itajaí SC MD

SUMMARY

At the moment 9 seemingly independent families with the clinical diagnosis of MJD are known in Brazil. The largest family tree of Azorean ancestry contatins 622 individuals in 9 generations. 236 were examined, 39 found to be affected by two examiners. Pheno-types I, II and III were expressed by 12, 23 and 4 patients with age of onset by phenotypea being 10-48, 14-54 and 30-55 respectively. Although clinically more severe, juvenile onset type I disease did not show as severe a ponto-mesencephialic atrophy on MRI as the father with type II disease of similar symptomatic duration. None of the 8 patients examined with MRI showed olivary atrophy or pallidal abnormalities. 12 affected and 23 at risk were evaluated with neuropsychological tests. Attention was normal in both groups. Verbal memory scores were below normal in the affected and there was greater decay with time than in the risk group. Both scored below normal in identifying silluettes and constructional praxis. Visual memory scores were well below normal for both, with many rotations but no omissions or confabulations. A peculiar pattern of multiplying internal details called «the fly-eye effect» was observed in 6 affected and 8 at risk. Defective color distinction when multiple colors presented close to each other, in face of proper naming of individual colors («color simultantagnosia»), was looked for in 29 people. 4/10 affected and 4/19 at risk showed this phenomenon. Cognitive dysfunctions in this MJD family are prominent in the sphere of vision. Whether they constitute an early manifestation in those at risk and thus serve as a clinical identifier of the illnes is yet to be established. Depression was looked for in the history of the family with DSM III-R criteria and an atempt at quantification with the Montgomery-Asberg Rating Scale. There was no significant quantitative difference between affected and at risk. Once undeniably symptomatic however, the patients had no, or less depression than themselves before or tat the early stages of the illness. Covert depression was appropriately excluded. Fully established MJD in this family seemed to exert a protective effect from depression.

Key words: Machado-Joseph disease, MRI, neuropsychology, visual memory, color naming, depression.

RESUMO

Há, até o momento, notícia de 9 famílias não aparentadas com o diagnóstico clínico de doença de Machado-Joseph (MJD) no Brasil. Esta é a maior família do mundo com a doença. É de origem açoriana e contém 622 indivíduos na árvore genealógica. Destes, 236 foram examinados. Dois examinadores julgaram 39 como afetados. Respectivamente 12, 23 e 4 pacientes tinham os fenôtipos I, II e III dia doença, com idades no início variando entre 10-48, 14-54 e 30-55. Doença tipo I de início juvenil não mostrou atrofia tão severa nas imagens por ressonância magnética (RM) quanto doença tipo II de duração igual, demonstrando que severidade clínica e grau de atrofia não caminham paralelamente. Nenhum dos 8 pacientes examinados por RM tinha atrofia olivar ou anormalidades no globo pálido. Doze pacientes e 23 sob risco foram submetidos a avaliiação neuropsicológica. A atenção foi normal em todos. Memória verbal estava pior nos doentes com maior decaimento com o tempo que nos sob risco. Ambos os grupos tiveram pontuação abaixo do normal na identificação de silhuetas e praxia construtiva. Memória visual estava bem abaixo do normal para ambos, com muitas rotações, porém sem omissões ou confabulação. Padrão peculiar de multiplicação dos detalhes internos, que denominamos o «efeito olho de mosca» foi visto em 6 doentes e 8 sob risco. Discriminação defeituosa de cores, quando múltiplas cores eram apresentadas liado a lado, na ausência de anomia ou cegueira a cores, caracterizável como «simultamagnosia a cores», surgiu como achado e foi pesquisada em 29 sujeitos. 4/10 doentes e 6/19 sob risco mostraram esta dificuldade. Conclui-se que disfunções cognitivas na esfera visual são proeminentes nesta família. Se seriam próprias da doença e manifestação precoce daqueles sob risco, está ainda para ser estabelecido. Depressão foi avaliada com critérios do DSM III-R e com o Montgomery-Asberg Depression Rating Scale. Não houve diferença entre doentes e sob risco. Entretanto, os pacientes tiveram menos depressão do que tinham tido antes ou nas fases precoces da doençta. A MJD plenamente instalada parecia exercer efeito protetor da depressão.

Palavras-chave: doença de Machado-Joseph, ressonância magnética, neuropsicologia, memória visual, distinção de cores, depressão.

Full text available only in PDF format.

Texto completo disponível apenas em PDF.

Aknowledgements We are indebted to the Hospital Israelita Albert Einstein of São Paulo for the MRI studies, the Hospital Marieta Konder of Itajai for providing the space for the clinics, Dr. Guy Rouleau of the Montreal General Hospital for the genetic studies, Dr. Patrick MacLeod from the University of Kingston, Ontario for his kind guidance, and the Hotel San Remo of Camboriu for their support.

Aceite: 20-agosto-1992

Dr. João Radvany Departamentos de Neurologia e Neuroimagem, Hospital Israelita Albert Einstein Av. Albert Einstein 627, conj. 389 05652-000 São Paulo SP Brasil.

1. Asberg M, Montgomery S, Perris C, Schalling D, Sedwall G. A comprehensive psycho-pathological rating scale. Acta Psychiat Scand 1978 (Suppl), 271:5-27.
2. Barbeau A, Roy M, Cunha L, de Vicente AN, Rosenberg RN, Nyhan WL MacLeod PL, Chazot G, Langston LB, Dawson DM, Coutinho P. The natural history of Machado-Joseph disease: an anylysis of 138 personally examined cases. Can J Neurol Sci 1984, 11:510-525.
3. Bergstedt J., Johansson M, Muller G. Hereditary spastic ataxia with central retinal degeneration and vestibular impairment: a clinical report on a family. Neurology 1962, 12:124-132.
4. Carson WJ, Radvany J, Farrer LA, Vincent D, Rosenberg RN, MacLeod PM, Rouleau GA. The Machado-Josep disease locus is different from the spinocerebellar ataxia locus (SCA1). Genomics 1992, 13:852-856.
5. Coutinho P. Neglected features of Machado-Joseph disease (Abstr) Research Initiatives in Machado-Joseph Disease. Bethesda MD: NINDS, June 3-4, 1991.
6. Coutinho P, Andrade C. Autosomal dominant system degeneration in Portuguese families of the Azores Islands: a new genetic disorder involving cerebellar, pyramidal, extrapyramidal and spinal cord motor functions. Neurology 1978, 28:703-709.
7. Coutinho P, Calheiros JM, Andrade C. Sobre uma nova doença degenerativa do sistema nervoso central transmitida de modo dominante e afectando famílias originárias dos Açores. (Nota prévia). O Médico 1977, 82:1-3.
8. Dawson DM, Feudo P, Zubick HH, Rosenberg R, Fowler H. Electrooculographic findings in Machado-Joseph disease. Neurology 1982, 32:1272-1276.
9. Foster JB, Ingram TTS. Familial cerebro-macular degeneration and ataxia. J Neurol Neurosurg Psychiatry 1962, 25:63-68.
10. Goto I, Tobimatsu S, Ohta M, Hosokawa S, Shibasaki H, Kuroiwa Y. Dentatorubropallydoluysian degeneration: clinical, neuro-ophtalmologic, biochemical and pathologic studies on autosomal form. Neurology 1982, 32:1395-1399.
11. Healton EB, Brust JCM, Kerr DR, Resor S, Penn A. Presumably Azorean disease in a presumably non-Azorean family. Neurology 1980, 30:1084-1089.
12. Iwabuchi K. Clinicopathological study on autosomal dominant forms of spinocerebellar degeneration (SCD) with special reference to Menzel's disease, hereditary ataxia linked to SCA1 and Japanese Machado-Joseph disease in Japan (Abstr). Research Initiatives in Machado-Joseph Disease. Bethesda MD: NINDS, June 3-4, 1991.
13. Jackson JF, Currier RD, Teriasaki PI, Morton NE. Spinocerebellar ataxia and HLS linkage: risk prediction by HLA typing. N Engl J Med 1977, 296:1138-1141.
14. Lezak MD: Neuropsychological assesment. New York: Oxford Univ Press, 1983.
15. Lima L, Coutinho P. Clinical criteria for diagnosis of Machado-Joseph disease: report of a non-Azorean family. Neurology 1980, 30:319-322.
16. Lisboa MFS, Mariotto GSS. Síndrome de Joseph: observação em uma família (Abstr). Arq Neuro-Psiquiat (São Paulo.) 1984 (Suppl), p 45.
17. Montgomery S, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979, 134:382-389.
18. Nákano KK, Dawson DM, Spence A. Machado disease: a hereditary ataxia in Portuguese immigrants to Massachusetts. Neurology 1972, 22:49-55.
19. Radvany J, Avila JO, Gabbai AA, Bacheschi LA. Doença de Machado-Joseph no Brasil: o relato das primeiras duas famílias (Abstr). Arq Neuro-Psiquiat (São Paulo) 1988 (Supl), 46B.
20. Romanul FCA, Fowler HL, Radvany J, Feldman RG, Feingold M. Azorean disease of the nervous system. N Engl J Med 1977, 296:1505-1508.
21. Romanul FCA, Radvany J, Fowler HL, Tarsy D. Azorean disease of the nervous system: report of six additional families (Abstr). Ann Neurol 1978, 4:183.
22. Rosenberg RN, Nyhan WL, Bay C, Shore P. Autosomal dominant striato-nigral degeneration: a clinical, pathological and biochemical study of a new genetic disorder. Neurology 1976, 26:703-714.
23. Sakai T, Ohta M, Ishino H. Joseph disease in a non-Portuguese family. Neurology 1983, 33:74-80.
24. Teive HAG, Arruda WO, Tevisol-Bittencourt PC. Doença de Machado-Joseph. Arq Neuro-Psiquiat (Sao Paulo) 1991, 49:172-179.
25. Wadia NH, Swami RK. A new form of heredofamilial spinocerebellar degeneration with slow eye movements (nine families). Brain 1971, 94:359-374.
26. Woods BT, Schaumburg HH. Nigro-spino-dentatal degeneration with nuclear ophtalmoplegia: a unique and partially treatable clinicopathological entity. J Neurol Sci 1972, 17:149-166.
27. Zoghbi HY, Pollack MS, Lyons LA, Ferrei RE, Daiger SP, Beaudet AL. Spinocerebellar ataxia: variable age of onset and linkage to human leukocyte antigen in a large kindred. Ann Neurol 1988, 23:580-584.

Machado-Joseph disease op azorean ancestry in Brazil: the Catarina kindred neurological, neuroimaging, psychiatric and neuropsychological findings in the largest known family, the «Catarina» kindred

Doenca de Machado-Joseph de ascendência dos Açores no Brasil: a linhagem Catarina. Achados neurológicos, de neuroimagem, psiquiátricos e neuropsicológicos na maior família conhecida, a linhagem «Catarina»

Publication Dates

Publication in this collection
19 Jan 2011
Date of issue
Mar 1993

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Asberg M, Montgomery S, Perris C, Schalling D, Sedwall G. A comprehensive psycho-pathological rating scale. Acta Psychiat Scand 1978 (Suppl), 271:5-27.

[2] 2. Barbeau A, Roy M, Cunha L, de Vicente AN, Rosenberg RN, Nyhan WL MacLeod PL, Chazot G, Langston LB, Dawson DM, Coutinho P. The natural history of Machado-Joseph disease: an anylysis of 138 personally examined cases. Can J Neurol Sci 1984, 11:510-525.

[3] 3. Bergstedt J., Johansson M, Muller G. Hereditary spastic ataxia with central retinal degeneration and vestibular impairment: a clinical report on a family. Neurology 1962, 12:124-132.

[4] 4. Carson WJ, Radvany J, Farrer LA, Vincent D, Rosenberg RN, MacLeod PM, Rouleau GA. The Machado-Josep disease locus is different from the spinocerebellar ataxia locus (SCA1). Genomics 1992, 13:852-856.

[5] 5. Coutinho P. Neglected features of Machado-Joseph disease (Abstr) Research Initiatives in Machado-Joseph Disease. Bethesda MD: NINDS, June 3-4, 1991.

[6] 6. Coutinho P, Andrade C. Autosomal dominant system degeneration in Portuguese families of the Azores Islands: a new genetic disorder involving cerebellar, pyramidal, extrapyramidal and spinal cord motor functions. Neurology 1978, 28:703-709.

[7] 7. Coutinho P, Calheiros JM, Andrade C. Sobre uma nova doença degenerativa do sistema nervoso central transmitida de modo dominante e afectando famílias originárias dos Açores. (Nota prévia). O Médico 1977, 82:1-3.

[8] 8. Dawson DM, Feudo P, Zubick HH, Rosenberg R, Fowler H. Electrooculographic findings in Machado-Joseph disease. Neurology 1982, 32:1272-1276.

[9] 9. Foster JB, Ingram TTS. Familial cerebro-macular degeneration and ataxia. J Neurol Neurosurg Psychiatry 1962, 25:63-68.

[10] 10. Goto I, Tobimatsu S, Ohta M, Hosokawa S, Shibasaki H, Kuroiwa Y. Dentatorubropallydoluysian degeneration: clinical, neuro-ophtalmologic, biochemical and pathologic studies on autosomal form. Neurology 1982, 32:1395-1399.

[11] 11. Healton EB, Brust JCM, Kerr DR, Resor S, Penn A. Presumably Azorean disease in a presumably non-Azorean family. Neurology 1980, 30:1084-1089.

[12] 12. Iwabuchi K. Clinicopathological study on autosomal dominant forms of spinocerebellar degeneration (SCD) with special reference to Menzel's disease, hereditary ataxia linked to SCA1 and Japanese Machado-Joseph disease in Japan (Abstr). Research Initiatives in Machado-Joseph Disease. Bethesda MD: NINDS, June 3-4, 1991.

[13] 13. Jackson JF, Currier RD, Teriasaki PI, Morton NE. Spinocerebellar ataxia and HLS linkage: risk prediction by HLA typing. N Engl J Med 1977, 296:1138-1141.

[14] 14. Lezak MD: Neuropsychological assesment. New York: Oxford Univ Press, 1983.

[15] 15. Lima L, Coutinho P. Clinical criteria for diagnosis of Machado-Joseph disease: report of a non-Azorean family. Neurology 1980, 30:319-322.

[16] 16. Lisboa MFS, Mariotto GSS. Síndrome de Joseph: observação em uma família (Abstr). Arq Neuro-Psiquiat (São Paulo.) 1984 (Suppl), p 45.

[17] 17. Montgomery S, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979, 134:382-389.

[18] 18. Nákano KK, Dawson DM, Spence A. Machado disease: a hereditary ataxia in Portuguese immigrants to Massachusetts. Neurology 1972, 22:49-55.

[19] 19. Radvany J, Avila JO, Gabbai AA, Bacheschi LA. Doença de Machado-Joseph no Brasil: o relato das primeiras duas famílias (Abstr). Arq Neuro-Psiquiat (São Paulo) 1988 (Supl), 46B.

[20] 20. Romanul FCA, Fowler HL, Radvany J, Feldman RG, Feingold M. Azorean disease of the nervous system. N Engl J Med 1977, 296:1505-1508.

[21] 21. Romanul FCA, Radvany J, Fowler HL, Tarsy D. Azorean disease of the nervous system: report of six additional families (Abstr). Ann Neurol 1978, 4:183.

[22] 22. Rosenberg RN, Nyhan WL, Bay C, Shore P. Autosomal dominant striato-nigral degeneration: a clinical, pathological and biochemical study of a new genetic disorder. Neurology 1976, 26:703-714.

[23] 23. Sakai T, Ohta M, Ishino H. Joseph disease in a non-Portuguese family. Neurology 1983, 33:74-80.

[24] 24. Teive HAG, Arruda WO, Tevisol-Bittencourt PC. Doença de Machado-Joseph. Arq Neuro-Psiquiat (Sao Paulo) 1991, 49:172-179.

[25] 25. Wadia NH, Swami RK. A new form of heredofamilial spinocerebellar degeneration with slow eye movements (nine families). Brain 1971, 94:359-374.

[26] 26. Woods BT, Schaumburg HH. Nigro-spino-dentatal degeneration with nuclear ophtalmoplegia: a unique and partially treatable clinicopathological entity. J Neurol Sci 1972, 17:149-166.

[27] 27. Zoghbi HY, Pollack MS, Lyons LA, Ferrei RE, Daiger SP, Beaudet AL. Spinocerebellar ataxia: variable age of onset and linkage to human leukocyte antigen in a large kindred. Ann Neurol 1988, 23:580-584.