Discinesias induzidas por levodopa em 176 pacientes com doença de Parkinson

Rocha, Maria Sheila G.; Andrade, Luiz Augusto F.; Ferraz, Henrique B.; Borges, Vanderci

doi:10.1590/S0004-282X1995000500004

Resumos

A ocorrência de discinesias dificulta consideravelmente o manuseio terapêutico dos pacientes parkinsonianos tratados com levodopa. Estudamos as características clínicas das discinesias em 176 pacientes com diagnóstico de doença de Parkinson e tratados com levodopa. As discinesias ocorreram, em média, após 6,2 anos de duração da doença e após 4,2 anos de tratamento com levodopa. A maioria dos pacientes (90%) achava-se nos estágios II e III de Hoehn & Yahr por ocasião do início das discinesias. As discinesias mais frequentes foram as de "pico de dose" e "contínua". Movimento do tipo distônico ocorreu em 40% dos casos e predominou nas discinesias de "fim de dose" e "bifásica". Distonia matinal correspondeu a 35% dos casos de distonia. Movimentos coreiformes se manifestaram de forma generalizada em 43,2% dos casos. Movimentos distônicos predominaram nos membros inferiores. A discinesia, quando unilateral, ocorreu mais frequüentemente no hemicorpo mais comprometido pela doença de Parkinson. A discinesia orofacial, quando isolada, foi mais frequente nos pacientes mais idosos.

doença de Parkinson; discinesias; levodopa

Dyskinesias are frequently observed in parkinsonian patients during levodopa treatment. The occurrence of these movement disorders usually makes the therapeutic management of the patients very difficult. The clinical characteristics of 176 patients with dyskinesias were retrospectively studied. Dyskinesias occurred, on average, after 6,2 years of duration of Parkinson's disease and after 4.2 years on treatment with levodopa. Patients were more likely to have dyskinesias during more advanced stages (measured by Hoehn and Yahr scale). Peak of dose and square wave were the types of dyskinesia more frequently described and were associated with choreic movements in most cases. Dystonia occurred in 40% of the cases and was predominant in end of dose and diphasic dyskinesias. Thirty-five percent of dystonia cases presented as "early morning dystonia". Chorea was the most frequent involuntary movement and mostly generalized. Dystonia was most commonly described in lower limbs. Orofacial dyskinesia, when occurred alone, was more frequently seen in old rather than young patients. When dyskinesia was unilateral it was more likely to occur in the side where Parkinson's disease was more severe.

Parkinson's disease; dyskinesias; levodopa

Discinesias induzidas por levodopa em 176 pacientes com doença de Parkinson

Levodopa-induced dyskinesias in 176 parkisonian patients

Maria Sheila G. Rocha^I; Luiz Augusto F. Andrade^II; Henrique B. Ferraz^III; Vanderci Borges^I

^IPós-graduanda em Neurologia. Setor de Investigação em Moléstias Extrapiramidais da Disciplina de Neurologia Clínica Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo, São Paulo

^IIProfessor Livre Docente, Chefe do Setor. Setor de Investigação em Moléstias Extrapiramidais da Disciplina de Neurologia Clínica Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo, São Paulo

^IIIDoutor em Neurologia, Médico do Setor de Investigação em Moléstias Extrapiramidais da Disciplina de Neurologia Clínica Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo, São Paulo

RESUMO

A ocorrência de discinesias dificulta consideravelmente o manuseio terapêutico dos pacientes parkinsonianos tratados com levodopa. Estudamos as características clínicas das discinesias em 176 pacientes com diagnóstico de doença de Parkinson e tratados com levodopa. As discinesias ocorreram, em média, após 6,2 anos de duração da doença e após 4,2 anos de tratamento com levodopa. A maioria dos pacientes (90%) achava-se nos estágios II e III de Hoehn & Yahr por ocasião do início das discinesias. As discinesias mais frequentes foram as de "pico de dose" e "contínua". Movimento do tipo distônico ocorreu em 40% dos casos e predominou nas discinesias de "fim de dose" e "bifásica". Distonia matinal correspondeu a 35% dos casos de distonia. Movimentos coreiformes se manifestaram de forma generalizada em 43,2% dos casos. Movimentos distônicos predominaram nos membros inferiores. A discinesia, quando unilateral, ocorreu mais frequüentemente no hemicorpo mais comprometido pela doença de Parkinson. A discinesia orofacial, quando isolada, foi mais frequente nos pacientes mais idosos.

Palavras-chave: doença de Parkinson, discinesias, levodopa.

SUMMARY

Dyskinesias are frequently observed in parkinsonian patients during levodopa treatment. The occurrence of these movement disorders usually makes the therapeutic management of the patients very difficult. The clinical characteristics of 176 patients with dyskinesias were retrospectively studied. Dyskinesias occurred, on average, after 6,2 years of duration of Parkinson's disease and after 4.2 years on treatment with levodopa. Patients were more likely to have dyskinesias during more advanced stages (measured by Hoehn and Yahr scale). Peak of dose and square wave were the types of dyskinesia more frequently described and were associated with choreic movements in most cases. Dystonia occurred in 40% of the cases and was predominant in end of dose and diphasic dyskinesias. Thirty-five percent of dystonia cases presented as "early morning dystonia". Chorea was the most frequent involuntary movement and mostly generalized. Dystonia was most commonly described in lower limbs. Orofacial dyskinesia, when occurred alone, was more frequently seen in old rather than young patients. When dyskinesia was unilateral it was more likely to occur in the side where Parkinson's disease was more severe.

Key words: Parkinson's disease, dyskinesias, levodopa.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

Agradecimentos - Agradecemos a CAPES pelo financiamento parcial deste estudo e ao Prof. Neil F. Novo (Departamento de Bioestatística da Escola Paulista de Medicina) pelo auxílio na análise estatística.

Aceite: l-junho-1995.

Dra. Maria Sheila G. Rocha - Rua Luís Gois 1328 apto 64 - 04043-150 São Paulo SP - Brasil.

1. Ballard PA, Tetrud JW, Langston JW. Permanent human parkinsonism due to l-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP): seven cases. Neurology 1985, 35:949-956.
2. Barbeau A. L-dopa therapy in Parkinson's disease: a critical review of nine years' experience. Can Med Assoc J 1969, 27:59-68.
3. Barbeau A. Parkinson's disease: clinical features and etiopathology. In Vinken PJ, Bruyn GW, Klawans HL (eds). Handbook of Clinical Neurology , Vol. 49: (Extrapyramidal disorders). New York: Elsevier, 1986, p87-152.
4. Bergmann KJ, Mendoza MR, Yahr MD. Parkinson's disease and long-term levodopa therapy. Adv Neurol 1986, 45:463-467.
5. Birkmayer W, Hornykiewicz O. Der 1-3,4-dihidroxyphenyIalanin (DOPA): Effekt bei der Parkinson-Akinese. Wien Klin Wschr 1961, 73:787-788.
6. Blin J, Bonnet A, Agid Y. Does levodopa aggravate Parkinson's disease? Neurology 1988, 38:1410-1416.
7. Cotzias GC, Van Woert MH, Schiffer LM. Aromatic amino acids and modification of parkinsonism. N Engl J Med 1967, 276:374-379.
8. Fahn S, Bressman SB. Should levodopatherapy for parkinsonism be started early or late? Evidence against early treatment. Can J Neurol Sci 1984, 11:200-206.
9. Friedman A. Levodopa-induced dyskinesia: clinical observations. J Neurol 1985, 232:29-31.
10. Gibb WRG, Lees AJ. A comparison of clinical and pathological features of young and old-onset Parkinson's disease. Neurology 1988, 38:1402-1406.
11. Granérus AK, Carlsson A, Svanborg A. The aging neuron: influence on symptomatology and therapeutic response in Parkinson's syndrome. Adv Neurol 1979, 24:327-334.
12. Horstink MWIM, Zijlmans JCM, Pasman HJ, Berger HJC, Van't Hof MA. Severity of Parkinson's disease is a risk factor for peak-dose dyskinesia. J Neurol Neurosurg Psychiatry 1990, 53:224-226.
13. Kidron D, Melamed E. Forms of dystonia in patients with Parkinson's disease. Neurology 1987, 37:1009-1011.
14. Kish S, Rajput A, Gilbert J. Distribution of striatal GABA in normal and parkinsonian brain [Abstr]. New York: VIII International Symposium on Parkinson's disease, 1985.
15. Kish SJ, Shannak HK, Hornykiewicz O. Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease: pathophysiologic and clinical implications. N Engl J Med 1988, 318:876-880.
16. Kostic V, Przedborski S, Flaster E, Sternic N. Early development of levodopa-induced dyskinesias and response fluctuations in young-onset Parkinson's disease. Neurology 1991, 41:202-205.
17. Künzle H. Bilateral projections from precentral motor cortex to the putamen and others parts of the basal ganglia: an autoradiographic study in Maccaca fascicularis. Brain Res 1975, 88:195-209.
18. Luquin MR, Scipioni O, Vaamonde J, Gershanik O, Obeso JA. Levodopa-induced dyskinesias in Parkinson's disease: clinical and pharmacological classification. Mov Disord 1992, 7:117-124.
19. Markham CH. The choreoathetoid movement disorder induced by levodopa. Clin Pharmacol Ther 1971, 12:340-346.
20. Marconi R, Lefebvre-Caparros D, Bonnet AM, Vidailhet M, Dubois B, Agid Y. Levodopa-induced dyskinesias in Parkinson's disease - phenomenology and pathophysiology. Mov Disord 1994, 9:2-12.
21. Marsden CD, Parkes JD, Quinn N. Fluctuactions of disability in Parkinson's disease: clinical aspects. In Marsden CD, Fahn S. (eds) Neurology 2: movement disorders. London: Butterworths, 1982, p. 96-122.
22. Melamed E. Early-morning dystonia. Arch Neurol 1979, 36:308-310.
23. Mones RJ, Elizan TS, Siegel GJ. Analysis of L-dopa induced dyskinesias in 51 patients with parkinsonism. J Neurol Neurosurg Psychiatry 1971, 34:668-673.
24. Mouradian MM, Heuser JE, Baronti F, Fabbrini G, Juncos JL, Chase TN. Pathogenesis of dyskinesias in Parkinson's disease. Ann Neurol 1989, 25:523-526.
25. Narabayashi H, Yokochi F, Nakajima Y. Levodopa-induced dyskinesia and thalamotomy. J Neurol Neurosurg Psychiatry 1984, 47:831-839.
26. Nausieda PA, Weiner WJ, Klawans HL. Dystonic foot response of parkinsonism. Arch Neurol 1980, 37:132-136.
27. Nutt JG. Levodopa-induced dyskinesia: review, observations, and speculations. Neurology 1990, 40:340-345.
28. Papavasiliou PS, Cotzias GC, Duby SE. Levodopa in parkinsonism: potentiation of central effects with a peripheral inhibitor. N Engl J Med 1972, 285:8-14.
29. Poewe WH, Lees AJ. The pharmacology of foot dystonia in parkinsonism. Clin Neuropharmacol 1987, 10:47-56.
30. Tolosa E, Alom J, Marti MJ. Drug induced dyskinesias. In Jankovic J, Tolosa E (eds).- Parkinson's disease and movement disorders. Ed 2. Baltimore: Williams & Wilkins, 1993, p.375-397.

Datas de Publicação

Publicação nesta coleção
08 Dez 2010
Data do Fascículo
Dez 1995

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

[1] 1. Ballard PA, Tetrud JW, Langston JW. Permanent human parkinsonism due to l-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP): seven cases. Neurology 1985, 35:949-956.

[2] 2. Barbeau A. L-dopa therapy in Parkinson's disease: a critical review of nine years' experience. Can Med Assoc J 1969, 27:59-68.

[3] 3. Barbeau A. Parkinson's disease: clinical features and etiopathology. In Vinken PJ, Bruyn GW, Klawans HL (eds). Handbook of Clinical Neurology , Vol. 49: (Extrapyramidal disorders). New York: Elsevier, 1986, p87-152.

[4] 4. Bergmann KJ, Mendoza MR, Yahr MD. Parkinson's disease and long-term levodopa therapy. Adv Neurol 1986, 45:463-467.

[5] 5. Birkmayer W, Hornykiewicz O. Der 1-3,4-dihidroxyphenyIalanin (DOPA): Effekt bei der Parkinson-Akinese. Wien Klin Wschr 1961, 73:787-788.

[6] 6. Blin J, Bonnet A, Agid Y. Does levodopa aggravate Parkinson's disease? Neurology 1988, 38:1410-1416.

[7] 7. Cotzias GC, Van Woert MH, Schiffer LM. Aromatic amino acids and modification of parkinsonism. N Engl J Med 1967, 276:374-379.

[8] 8. Fahn S, Bressman SB. Should levodopatherapy for parkinsonism be started early or late? Evidence against early treatment. Can J Neurol Sci 1984, 11:200-206.

[9] 9. Friedman A. Levodopa-induced dyskinesia: clinical observations. J Neurol 1985, 232:29-31.

[10] 10. Gibb WRG, Lees AJ. A comparison of clinical and pathological features of young and old-onset Parkinson's disease. Neurology 1988, 38:1402-1406.

[11] 11. Granérus AK, Carlsson A, Svanborg A. The aging neuron: influence on symptomatology and therapeutic response in Parkinson's syndrome. Adv Neurol 1979, 24:327-334.

[12] 12. Horstink MWIM, Zijlmans JCM, Pasman HJ, Berger HJC, Van't Hof MA. Severity of Parkinson's disease is a risk factor for peak-dose dyskinesia. J Neurol Neurosurg Psychiatry 1990, 53:224-226.

[13] 13. Kidron D, Melamed E. Forms of dystonia in patients with Parkinson's disease. Neurology 1987, 37:1009-1011.

[14] 14. Kish S, Rajput A, Gilbert J. Distribution of striatal GABA in normal and parkinsonian brain [Abstr]. New York: VIII International Symposium on Parkinson's disease, 1985.

[15] 15. Kish SJ, Shannak HK, Hornykiewicz O. Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease: pathophysiologic and clinical implications. N Engl J Med 1988, 318:876-880.

[16] 16. Kostic V, Przedborski S, Flaster E, Sternic N. Early development of levodopa-induced dyskinesias and response fluctuations in young-onset Parkinson's disease. Neurology 1991, 41:202-205.

[17] 17. Künzle H. Bilateral projections from precentral motor cortex to the putamen and others parts of the basal ganglia: an autoradiographic study in Maccaca fascicularis. Brain Res 1975, 88:195-209.

[18] 18. Luquin MR, Scipioni O, Vaamonde J, Gershanik O, Obeso JA. Levodopa-induced dyskinesias in Parkinson's disease: clinical and pharmacological classification. Mov Disord 1992, 7:117-124.

[19] 19. Markham CH. The choreoathetoid movement disorder induced by levodopa. Clin Pharmacol Ther 1971, 12:340-346.

[20] 20. Marconi R, Lefebvre-Caparros D, Bonnet AM, Vidailhet M, Dubois B, Agid Y. Levodopa-induced dyskinesias in Parkinson's disease - phenomenology and pathophysiology. Mov Disord 1994, 9:2-12.

[21] 21. Marsden CD, Parkes JD, Quinn N. Fluctuactions of disability in Parkinson's disease: clinical aspects. In Marsden CD, Fahn S. (eds) Neurology 2: movement disorders. London: Butterworths, 1982, p. 96-122.

[22] 22. Melamed E. Early-morning dystonia. Arch Neurol 1979, 36:308-310.

[23] 23. Mones RJ, Elizan TS, Siegel GJ. Analysis of L-dopa induced dyskinesias in 51 patients with parkinsonism. J Neurol Neurosurg Psychiatry 1971, 34:668-673.

[24] 24. Mouradian MM, Heuser JE, Baronti F, Fabbrini G, Juncos JL, Chase TN. Pathogenesis of dyskinesias in Parkinson's disease. Ann Neurol 1989, 25:523-526.

[25] 25. Narabayashi H, Yokochi F, Nakajima Y. Levodopa-induced dyskinesia and thalamotomy. J Neurol Neurosurg Psychiatry 1984, 47:831-839.

[26] 26. Nausieda PA, Weiner WJ, Klawans HL. Dystonic foot response of parkinsonism. Arch Neurol 1980, 37:132-136.

[27] 27. Nutt JG. Levodopa-induced dyskinesia: review, observations, and speculations. Neurology 1990, 40:340-345.

[28] 28. Papavasiliou PS, Cotzias GC, Duby SE. Levodopa in parkinsonism: potentiation of central effects with a peripheral inhibitor. N Engl J Med 1972, 285:8-14.

[29] 29. Poewe WH, Lees AJ. The pharmacology of foot dystonia in parkinsonism. Clin Neuropharmacol 1987, 10:47-56.

[30] 30. Tolosa E, Alom J, Marti MJ. Drug induced dyskinesias. In Jankovic J, Tolosa E (eds).- Parkinson's disease and movement disorders. Ed 2. Baltimore: Williams & Wilkins, 1993, p.375-397.