Tratamento da doença de Meige com droga agonista de receptores GABA

Andrade, Luiz Augusto Franco de; Bertolucci, Paulo Henrique Ferreira

doi:10.1590/S0004-282X1985000300004

Resumos

A doença de Meige é distúrbio de movimento que consiste no aparecimento espontâneo de blefarospasmo associado a movimentos distônicos de musculatura orofacial. Associadamene podem ser encontrados torcicolo espasmódico, disfonia espástica e distonia de extremidades. Várias hipóteses foram formuladas para explicar esse distúrbio, tendo em vista a resposta a drogas com ação conhecida nos sistemas de neurotransmissores do cérebro. Algumas evidências apontam para um estado de preponderância dopaminérgica e, nesse sentido, justifica-se a estimulação da atividade GABA, sabendo-se que esse neurotrans-missor age sobre uma das alças de controle da produção de dopamina na substância negra. Por essa razão investigamos a ação de um agonista GABA, o baclofen, sobre a doença de Meige. Foram incluídos no protocolo 5 pacientes, 4 mulheres e um homem, com idade variando entre 50 e 63 anos e duração da doença variando entre 4 meses e 18 anos. Todos apresentavam blefaros-pasmo-distonia orofacial e, além disso três apresentavam disfonia espástica e um distonia de extremidades. A droga era iniciada em dose de 20mg/dia, aumentada em lOmg a cada três dias até ser obtida resposta ou surgirem efeitos colaterais. Um dos pacientes apresentou melhora marcada do blefaros-pasmo-distonia orofacial e outro melhora moderada dos mesmos sintomas, em avaliação 30 dias após estabilização da dose. Não houve melhora da disfonia espástica e ocorreu melhora moderada da distonia de extremidades. Não podemos afirmar que a melhora observada ao fim de um mês se mantenha, ou mesmo que melhora mais significativa fosse observada em avaliação feita mais tardiamente. Concluimos que o baclofen pode ser útil, pelo menos por algum tempo, na doença de Meige.

The spontaneous occurence of blepharospasm and dystonic movements in face muscles, particularly those of the perioral and mandibular regions, has been named Meige's disease. Other dystonic features as spasmodic torticollis, dysphagia, spasmodic dysphonia and segmental dystonia of the limbs may, eventually, be present in the same patient. There is very little knowledge about the pathology of this disease. Many hypotheses concerning the pathophysiology of this entity have been put forward, most of them correlating the clinical response to several drugs with known action on the neurotransmitter system of the brain. There are some evidences that it may exist a dopaminergic preponderance in the disease. In the nigro-striatal pathway, one of the retrograde loops in the feed-back control of dopamine synthesis by nigral neurons is dependent on GABA. Increasing GABA activity through GABA agonists that cross the blood-brain barrier could result in a decreased dopaminergic action in the nigro-striatal pathway and, thus, ameliorate the dystonic symptoms which might have been produced by its increased function. We have used baclofen, a GABA-agonist drug, to treat five patients with Meige's disease, in a single-blinded trial. These were four females and one male, with age ranging from 50 to 63 years. The drug was started at 20mg/day, being increased by 10mg each three days reaching a maximum dose of 70mg/day. One of the patients showed marked improvement of blepharospasm and orofacial dystonia and a second patient had a moderate improvement in the same symptoms. Another patient showed moderate improvement of limb dystonia, but had no benefit in the facial movements. None of the three patients who suffered from spasmodic disphonia, aside from the classical signs, improved the speech problem. The results obtained were analyzed 30 days after the start of the drug. We are not able to state if the clinical response will be further maintained or, even, if more time was given until the clinical assesment was made, better results would came up. The conclusion is that baclofen may be useful to some patients suffering from Meige's disease, at least for some time.

Tratamento da doença de Meige com droga agonista de receptores GABA

Treatment of Meige's disease with GABA-receptor agonist drug

Luiz Augusto Franco de Andrade^I; Paulo Henrique Ferreira Bertolucci^II

^IProfessor Adjunto, Doutor em Neurologia. Setor de Investigação em Moléstias Extrapiramidais da Disciplina de Neurologia da Escola Paulista de Medicina

^IIPós-graduando. Setor de Investigação em Moléstias Extrapiramidais da Disciplina de Neurologia da Escola Paulista de Medicina

RESUMO

A doença de Meige é distúrbio de movimento que consiste no aparecimento espontâneo de blefarospasmo associado a movimentos distônicos de musculatura orofacial. Associadamene podem ser encontrados torcicolo espasmódico, disfonia espástica e distonia de extremidades. Várias hipóteses foram formuladas para explicar esse distúrbio, tendo em vista a resposta a drogas com ação conhecida nos sistemas de neurotransmissores do cérebro. Algumas evidências apontam para um estado de preponderância dopaminérgica e, nesse sentido, justifica-se a estimulação da atividade GABA, sabendo-se que esse neurotrans-missor age sobre uma das alças de controle da produção de dopamina na substância negra. Por essa razão investigamos a ação de um agonista GABA, o baclofen, sobre a doença de Meige. Foram incluídos no protocolo 5 pacientes, 4 mulheres e um homem, com idade variando entre 50 e 63 anos e duração da doença variando entre 4 meses e 18 anos. Todos apresentavam blefaros-pasmo-distonia orofacial e, além disso três apresentavam disfonia espástica e um distonia de extremidades. A droga era iniciada em dose de 20mg/dia, aumentada em lOmg a cada três dias até ser obtida resposta ou surgirem efeitos colaterais. Um dos pacientes apresentou melhora marcada do blefaros-pasmo-distonia orofacial e outro melhora moderada dos mesmos sintomas, em avaliação 30 dias após estabilização da dose. Não houve melhora da disfonia espástica e ocorreu melhora moderada da distonia de extremidades. Não podemos afirmar que a melhora observada ao fim de um mês se mantenha, ou mesmo que melhora mais significativa fosse observada em avaliação feita mais tardiamente. Concluimos que o baclofen pode ser útil, pelo menos por algum tempo, na doença de Meige.

SUMMARY

The spontaneous occurence of blepharospasm and dystonic movements in face muscles, particularly those of the perioral and mandibular regions, has been named Meige's disease. Other dystonic features as spasmodic torticollis, dysphagia, spasmodic dysphonia and segmental dystonia of the limbs may, eventually, be present in the same patient. There is very little knowledge about the pathology of this disease. Many hypotheses concerning the pathophysiology of this entity have been put forward, most of them correlating the clinical response to several drugs with known action on the neurotransmitter system of the brain. There are some evidences that it may exist a dopaminergic preponderance in the disease. In the nigro-striatal pathway, one of the retrograde loops in the feed-back control of dopamine synthesis by nigral neurons is dependent on GABA. Increasing GABA activity through GABA agonists that cross the blood-brain barrier could result in a decreased dopaminergic action in the nigro-striatal pathway and, thus, ameliorate the dystonic symptoms which might have been produced by its increased function. We have used baclofen, a GABA-agonist drug, to treat five patients with Meige's disease, in a single-blinded trial. These were four females and one male, with age ranging from 50 to 63 years. The drug was started at 20mg/day, being increased by 10mg each three days reaching a maximum dose of 70mg/day. One of the patients showed marked improvement of blepharospasm and orofacial dystonia and a second patient had a moderate improvement in the same symptoms. Another patient showed moderate improvement of limb dystonia, but had no benefit in the facial movements. None of the three patients who suffered from spasmodic disphonia, aside from the classical signs, improved the speech problem. The results obtained were analyzed 30 days after the start of the drug. We are not able to state if the clinical response will be further maintained or, even, if more time was given until the clinical assesment was made, better results would came up. The conclusion is that baclofen may be useful to some patients suffering from Meige's disease, at least for some time.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

Trabalho do Setor de Investigação em Moléstias Extrapiramidais da Disciplina de Neurologia da Escola Paulista de Medicina.

Agradecimento: Os autores agradecem ao Laboratório Ciba-Geigy pelo fornecimento da droga utilizada no estudo.

Disciplina de Neurologia, Departamento de Neurologia e Neurocirurgia, Escola Paulista de Medicina - Rua Botucatu, 740 - 04023, São Paulo, SP - Brasil.

1. ALTROCCHI, RH. - Spontaneous oral-facial dyskinesia. Arch. Neurol. 26:506, 1972.
2. BRENNAN, M.J.W.; RUFF, P.; SANDYK, R. - Efficacy of a combination of sodium valproate and baclofen in Meige's disease (idiopathic oro-facial dystonia). Brit. med. J. 285:853, 1982.
3. CASEY, D.E. - Pharmacology of blepharospasm-oromandibular dystonia syndrome. Neurology 30:690, 1980.
4. FAHN, S.; BRENNAN, S.; BURKE, R.; HENING, W.; ILSON, J. & WALTERS, A. - Treatment of blepharospasm with high-dose baclofen. Ann. Neurol. 14:112, 1983.
5. GARCIA-ALBEA, E.; FRANCH, O.; MUNOZ, D. & RICOY, J.R. - Brueghel's syndrome: report of a case with postmortem studies. J. Neurol. Neurosurg. Psychiat. 44:437, 1981.
6. GRANACHER, R.P. - Facial dyskinesia after antihistamines. N. Engl. J. Med. 296:516, 1977.
7. JANKOVTC, J. - Treatment of hyperkinetic movement disorders with tetrabenazine: a double-blind crossover study. Ann. Neurol. 11:41, 1982.
8. JANKOVTC, J. & FORD, J. - Blepharospasm and oro-facial-cervical dystonia: clinical and pharmacological findings in 100 patients. Ann. Neurol. 13:402, 1983.
9. JANKOVTC, J. & PATEL, S.C. - Blepharospasm associated with brainstem lesions. Neurology 33:1237, 1983.
10. MARSDEN, CD. - Blepharospasm-oromandibular dystonia syndrome (Brueghel's syndrome). A variant of adult-onset torsion dystonia? J. Neurol. Neurosurg. Psychiat. 39:1204, 1976.
11. MARSDEN, CD. & SHEEHY, M.P. - GABA and movement disorders. Adv. Biochem. Psychopharmac. 30:225, 1982.
12. MEIGE, H. - Les convulsions de la face. Une forme clinique de convulsion faciale bilatérale et médiane. Rev. Neurol. (Paris) 20:437, 1910.
13. MICHELI, F.; FERNANDEZ PARDAL, M.M. & LEIGUARDA, R.C - Beneficial effects of lisuride in Meige disease. Neurology 32:432, 1982.
14. NEOPHYTIDES, A.; SURIA, A. & CHASE, T.N. - Cerebrospinal fluid GABA in neurological disease. Neurology 28:359, 1978.
15. NUTT, J.G.; HAMMERSTAD, J.P.; de GARMO, P. & CARTER, J. - Cranial dystonia: double-blind crossover study of anticholinergics. Neurology 34:215, 1984.
16. PAULSON, G.W. - Meige's syndrome. Geriatrics 27:69, 1972.
17. POMPEU, F.J.B.C. - Forma juvenil da síndrome de Brueghel-Marsden (Blefarospasmo e distonia oromandibular). Tese. Faculdade de Ciências Médicas da Universidade Estadual do Rio de Janeiro. Rio de Janeiro, 1979.
18. POWERS, J.M. - Descongestant-induced blepharospasm and orofacial dystonia. J. amer. med. Assoc. 247:3244, 1982.
19. RUBIN, E.H. & WOOTEN, G.F. - Neuroleptic but not denervation-induced dopamine supersensitivity is blocked by lithium. Neurology 32:265, 1982.
20. SNIDER, S.R. & CONSROE, P. - Treatment of Meige syndrome with cannabidiol. Neurology 34 (supp. 1):147, 1984.
21. STAHL, S.M. & BERGER, P.A. - Bromocriptine, physostigmine and neurotransmitter mechanisms in the dystonias. Neurology 32:889, 1982.
22. STAHL, S.M.; YESAVAGE, J.A. & BERGER, P.A. - Pharmacologic characteristics of Meige dystonia: differentiation from tardive dyskinesia. J. clin. Psychiat. 43:445, 1982.
23. TANNER, C.M.; GLANTZ, R.H. & KLAWANS, H.L. - Meige disease: acute and chronic cholinergic effects. Neurology 32:783, 1982.
24. THATCH, B.T.; CHASE, T.N. & BOSMA, J.F. - Oral-facial dyskinesia associated with prolonged use of antihistamine decongestants. N. Engl. J. Med. 293:486, 1975.
25. TOLOSA, E.S. - Clinical features of Meige's disease (idiopathic orofacial dystonia). A report of 17 cases. Arch. Neurol. 38:147, 1981.
26. TOLOSA, E.S. & LAI, C. - Meige disease: striatal dopaminergic preponderance. Neurology 29:1126, 1979.
27. WEINER, W.J. .& NAUSIEDA, P.A. - Meige's syndrome during long-term dopaminergic therapy in Parkinson's disease. Arch. Neurol. 39:451, 1982.

Datas de Publicação

Publicação nesta coleção
13 Ago 2012
Data do Fascículo
Set 1985

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

[1] 1. ALTROCCHI, RH. - Spontaneous oral-facial dyskinesia. Arch. Neurol. 26:506, 1972.

[2] 2. BRENNAN, M.J.W.; RUFF, P.; SANDYK, R. - Efficacy of a combination of sodium valproate and baclofen in Meige's disease (idiopathic oro-facial dystonia). Brit. med. J. 285:853, 1982.

[3] 3. CASEY, D.E. - Pharmacology of blepharospasm-oromandibular dystonia syndrome. Neurology 30:690, 1980.

[4] 4. FAHN, S.; BRENNAN, S.; BURKE, R.; HENING, W.; ILSON, J. & WALTERS, A. - Treatment of blepharospasm with high-dose baclofen. Ann. Neurol. 14:112, 1983.

[5] 5. GARCIA-ALBEA, E.; FRANCH, O.; MUNOZ, D. & RICOY, J.R. - Brueghel's syndrome: report of a case with postmortem studies. J. Neurol. Neurosurg. Psychiat. 44:437, 1981.

[6] 6. GRANACHER, R.P. - Facial dyskinesia after antihistamines. N. Engl. J. Med. 296:516, 1977.

[7] 7. JANKOVTC, J. - Treatment of hyperkinetic movement disorders with tetrabenazine: a double-blind crossover study. Ann. Neurol. 11:41, 1982.

[8] 8. JANKOVTC, J. & FORD, J. - Blepharospasm and oro-facial-cervical dystonia: clinical and pharmacological findings in 100 patients. Ann. Neurol. 13:402, 1983.

[9] 9. JANKOVTC, J. & PATEL, S.C. - Blepharospasm associated with brainstem lesions. Neurology 33:1237, 1983.

[10] 10. MARSDEN, CD. - Blepharospasm-oromandibular dystonia syndrome (Brueghel's syndrome). A variant of adult-onset torsion dystonia? J. Neurol. Neurosurg. Psychiat. 39:1204, 1976.

[11] 11. MARSDEN, CD. & SHEEHY, M.P. - GABA and movement disorders. Adv. Biochem. Psychopharmac. 30:225, 1982.

[12] 12. MEIGE, H. - Les convulsions de la face. Une forme clinique de convulsion faciale bilatérale et médiane. Rev. Neurol. (Paris) 20:437, 1910.

[13] 13. MICHELI, F.; FERNANDEZ PARDAL, M.M. & LEIGUARDA, R.C - Beneficial effects of lisuride in Meige disease. Neurology 32:432, 1982.

[14] 14. NEOPHYTIDES, A.; SURIA, A. & CHASE, T.N. - Cerebrospinal fluid GABA in neurological disease. Neurology 28:359, 1978.

[15] 15. NUTT, J.G.; HAMMERSTAD, J.P.; de GARMO, P. & CARTER, J. - Cranial dystonia: double-blind crossover study of anticholinergics. Neurology 34:215, 1984.

[16] 16. PAULSON, G.W. - Meige's syndrome. Geriatrics 27:69, 1972.

[17] 17. POMPEU, F.J.B.C. - Forma juvenil da síndrome de Brueghel-Marsden (Blefarospasmo e distonia oromandibular). Tese. Faculdade de Ciências Médicas da Universidade Estadual do Rio de Janeiro. Rio de Janeiro, 1979.

[18] 18. POWERS, J.M. - Descongestant-induced blepharospasm and orofacial dystonia. J. amer. med. Assoc. 247:3244, 1982.

[19] 19. RUBIN, E.H. & WOOTEN, G.F. - Neuroleptic but not denervation-induced dopamine supersensitivity is blocked by lithium. Neurology 32:265, 1982.

[20] 20. SNIDER, S.R. & CONSROE, P. - Treatment of Meige syndrome with cannabidiol. Neurology 34 (supp. 1):147, 1984.

[21] 21. STAHL, S.M. & BERGER, P.A. - Bromocriptine, physostigmine and neurotransmitter mechanisms in the dystonias. Neurology 32:889, 1982.

[22] 22. STAHL, S.M.; YESAVAGE, J.A. & BERGER, P.A. - Pharmacologic characteristics of Meige dystonia: differentiation from tardive dyskinesia. J. clin. Psychiat. 43:445, 1982.

[23] 23. TANNER, C.M.; GLANTZ, R.H. & KLAWANS, H.L. - Meige disease: acute and chronic cholinergic effects. Neurology 32:783, 1982.

[24] 24. THATCH, B.T.; CHASE, T.N. & BOSMA, J.F. - Oral-facial dyskinesia associated with prolonged use of antihistamine decongestants. N. Engl. J. Med. 293:486, 1975.

[25] 25. TOLOSA, E.S. - Clinical features of Meige's disease (idiopathic orofacial dystonia). A report of 17 cases. Arch. Neurol. 38:147, 1981.

[26] 26. TOLOSA, E.S. & LAI, C. - Meige disease: striatal dopaminergic preponderance. Neurology 29:1126, 1979.

[27] 27. WEINER, W.J. .& NAUSIEDA, P.A. - Meige's syndrome during long-term dopaminergic therapy in Parkinson's disease. Arch. Neurol. 39:451, 1982.