Chronic progressive external ophthalmoplegia: I. A quantitative histochemical study of skeletal muscles

Dias-Tosta, Elza

doi:10.1590/S0004-282X1988000200004

Abstracts

This study quantitates the major morphological and cytochemical changes in limb muscle biopsies from 37 patients with the, syndrome of chronic progressive external ophthalmoplegia (CPEO). The aim was to assess the value of limb muscle biopsy in the diagnosis of this syndrome; to define the myopathological changes and to determine whether there were any specific clinico-pathological correlations. Patients were divided into three clinical groups - 11 patients with CPEO with facial and/or limb muscle weakness; 10 with CPEO with facial and/or limb muscle weakness and a positive family history; 16 with CPEO with one or more of the following: pigmentary retinopathy, cerebellar ataxia, pyramidal signs and peripheral neuropathy. The following parameters were measured: the proportions of histochemical fibre types, the muscle fibre areas and the percentage of muscle fibres showing increased oxidative enzyme activity. Pooled results for each of the clinical categories were compared. Statistical analysis of fibre areas and the percentage of fibres with increased oxidative enzyme activity, showed that group 2 differed from the others (p < 0.05). Patients in group 2 showed the highest incidence of type 1 fibre hypertrophy, type 2A atrophy and the lowest incidence of fibres with increased oxidative activity. Fibre type disproportions occurred in all three groups but the differences were not significant.

Estudaram-se quantitativamente as alterações morfológicas e histoquímicas de biópsias de músculos dos membros superiores ou inferiores em 37 pacientes com a síndrome de oftalmoplegia externa crônica e progressiva (OECP). O objetivo era determinar o valor da biópsia do músculo esquelético dos membros no diagnóstico desta síndrome, definir as alterações miopatológicas e determinar se havia alguma correlação clínico-patológica específica. Os pacientes foram classificados em três grupos clínicos: 11 pacientes com OECP mais fraqueza de musculatura facial e/ou de membros; 10 pacientes com OECP, fraqueza muscuiar e história familiar positiva; 16 pacientes com OECP, fraqueza muscular e um ou mais dos seguintes sinais - retinopatia pigmentar, ataxia cerebelar, sinais piramidais e neuropatia periférica. Os seguintes parâmetros foram avaliados: proporção de tipos histoquímicos de fibras musculares, áreas destas fibras, percentagem de fibras mostrando aumento de atividade enzimática oxidativa. Os resultados foram comparados entre os três grupos definidos clinicamente. Análises estatísticas das áreas das fibras e da percentagem de fibras com aumento da atividade enzimática oxidativa, mostram que o grupo 2 difere dos demais (p < 0,05). Os pacientes do grupo 2 mostraram a mais alta incidência de hipertrofia de fibras do tipo 1, atrofia do tipo 2A e a mais baixa incidência de fibras com aumento da atividade oxidativa. A desproporção de tipos de fibras ocorreu nos três grupos, mas sem diferença significativa.

Elza Dias-Tosta

M.D., Ph.D. - Muscle Histochemistry Laboratory, National Hospital for Nervous Diseases, University of London, Queen Square, London, England

SUMMARY

This study quantitates the major morphological and cytochemical changes in limb muscle biopsies from 37 patients with the, syndrome of chronic progressive external ophthalmoplegia (CPEO). The aim was to assess the value of limb muscle biopsy in the diagnosis of this syndrome; to define the myopathological changes and to determine whether there were any specific clinico-pathological correlations. Patients were divided into three clinical groups - 11 patients with CPEO with facial and/or limb muscle weakness; 10 with CPEO with facial and/or limb muscle weakness and a positive family history; 16 with CPEO with one or more of the following: pigmentary retinopathy, cerebellar ataxia, pyramidal signs and peripheral neuropathy. The following parameters were measured: the proportions of histochemical fibre types, the muscle fibre areas and the percentage of muscle fibres showing increased oxidative enzyme activity. Pooled results for each of the clinical categories were compared. Statistical analysis of fibre areas and the percentage of fibres with increased oxidative enzyme activity, showed that group 2 differed from the others (p < 0.05). Patients in group 2 showed the highest incidence of type 1 fibre hypertrophy, type 2A atrophy and the lowest incidence of fibres with increased oxidative activity. Fibre type disproportions occurred in all three groups but the differences were not significant.

RESUMO

Estudaram-se quantitativamente as alterações morfológicas e histoquímicas de biópsias de músculos dos membros superiores ou inferiores em 37 pacientes com a síndrome de oftalmoplegia externa crônica e progressiva (OECP). O objetivo era determinar o valor da biópsia do músculo esquelético dos membros no diagnóstico desta síndrome, definir as alterações miopatológicas e determinar se havia alguma correlação clínico-patológica específica. Os pacientes foram classificados em três grupos clínicos: 11 pacientes com OECP mais fraqueza de musculatura facial e/ou de membros; 10 pacientes com OECP, fraqueza muscuiar e história familiar positiva; 16 pacientes com OECP, fraqueza muscular e um ou mais dos seguintes sinais - retinopatia pigmentar, ataxia cerebelar, sinais piramidais e neuropatia periférica. Os seguintes parâmetros foram avaliados: proporção de tipos histoquímicos de fibras musculares, áreas destas fibras, percentagem de fibras mostrando aumento de atividade enzimática oxidativa. Os resultados foram comparados entre os três grupos definidos clinicamente. Análises estatísticas das áreas das fibras e da percentagem de fibras com aumento da atividade enzimática oxidativa, mostram que o grupo 2 difere dos demais (p < 0,05). Os pacientes do grupo 2 mostraram a mais alta incidência de hipertrofia de fibras do tipo 1, atrofia do tipo 2A e a mais baixa incidência de fibras com aumento da atividade oxidativa. A desproporção de tipos de fibras ocorreu nos três grupos, mas sem diferença significativa.

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Acknowledgements - I am grateful to Dr. J.A. Morgan-Hughes and Dr. D.N. Landon for their constant interest and helpful criticism during the preparation of this work, and also made available to me the laboratory facilities in their departments. I also like to thank Dr. A. Pullen and Miss E. Paul for their helps with the statistics, Miss M. Ellison for excelent technical assistance. Dr. Tosta was supported during preparation of this work by the Brazilian Government.

Unidade de Neurologia, Hospital de Base do Distrito Federal - 70000 Brasília DF - Brasil.

1. Bernat JL, Ochoa JL - Muscle hypertrophy after partial denervation: a human case. J Neurol Neurosurg Psychiat 41: 719, 1978.
2. Brooke MH, Engel WK - The histographic analysis of human muscle biopsies with regard to fibre types: 1. Adult male and female. Neurology 19: 221, 1969.
3. Brooke MH, Engel WK - The histographic analysis of human muscle biopsies with regard to fibre types: 2. Diseases of the upper and lower motor neuron. Neurology 19: 378, 1969.
4. Brooke MH, Kaiser KK - Muscie fibre types: how many and what kind? Arch Neurol 23: 369, 1970.
5. Brooke MH, Kaiser KK - Three «Myosin Adenosine Triphosphatase» systems: the nature of their pH lability and sulphydryl dependence. J Histochem Cytochem 18: 670, 1970.
6. Buller AJ, Pope R - Plasticity in mammalian skeletal muscle. Philos Soc London (Biol) 278: 295, 1977.
7. Castaigne P, Laplane D, Fardeau M, Dordain G, Autret A, Hirt L - Myopathie avec anomalies mitochondriales localisées aux fibres de type 1: documents cliniques, histo-chimiques et ultrastructuraux concernant une forme atrophique diffuse à debut oculaire. Rev Neurol 126: 81, 1972.
8. Dubowitz V, Brooke MH - Muscle Biopsy: a Modern Approach. Saunders, Philadelphia, 1973.
9. Engel WK - «Ragged-red fibres» in ophthalmoplegia syndromes and their differential diagnosis. In: Abstracts of the Second International Congress on Muscle Diseases. Excerpta Medica, Amsterdam, 1971, pg 28.
10. Engel WK, Cunninghan CG - Rapid examination of muscle tissue: an improved trichrome method for rapid diagnosis of muscle biopsy fresh frozen section. Neurology 13: 919, 1963.
11. Jansson E, Syodin B, Tesch P - Changes in muscle fibre type distribution in man after physical training. Acta Physiol Scand 104: 235, 1978.
12. Lambert CD - Uniform muscle histochemistry: a clinical and biopsy study. Trans Am Neurol Assoc 99: 57. 1974.
13. Lömo T - The role of activity in the control of membrane and contractile properties of skeletal muscle. In: Thesleff S (ed): Motor Innervation of Muscle. Academic Press, New York, 1976, pg 289.
14. Maunder-Sewry CA, Dubowitz V. - Needle muscle biopsy for carrier detection in Duchenne muscular dystrophy: 1. Light microscopy, histology, histochemistry and quantitation. J Neurol Sci 305, 1981.
15. Morgan-Hughes JA, Mair WGP - Atypical muscle mitochondria in oculoskeletal myopathy. Brain 96: 215, 1973.
16. Munsat TL, McNeal D, Waters R - Effects of nerve stimulation of human muscle. Arch Neurol 33: 608, 1976.
17. Nachlas MM, Tsou KC, de Souza E, Cheng CS, Seligman AM - Cytochemical demonstration of succinic dehydrogenase by the use of a new p-nitrophenyl substituted dite-trazole. J Histochem Cytochem 5: 420, 1957.
18. Novikoff AB, Shin MY, Drucker J - Mitochondrial localization of oxidative enzymes: staining results with two tetrazolium salts. J Biophys Biochem Cytol 9: 47, 1961.
19. Olson W, Engel WK, Walsh GO, Einaugler R - Oculocraniosomatic neuromuscular disease with «ragged-red» fibres: histochemical and ultrastructural changes in limb muscles of a group of patients with idiopathic progressive external ophthalmoplegia. Arch Neurol 26: 193, 1972.
20. Wattenberg LW, Leong JL - Effects of coenzyme Q₁₀ and menadione succinic dehydrogenase activity as measured by tetrazolium salt reduction. J Histochem Cytochem 8: 296, 1960.

Chronic progressive external ophthalmoplegia: I. A quantitative histochemical study of skeletal muscles

Oftalmoplegia externa crônica progressiva: I. Estudo histoquímico quantitativo de músculos esqueléticos

Publication Dates

Publication in this collection
21 June 2011
Date of issue
June 1988

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

[1] 1. Bernat JL, Ochoa JL - Muscle hypertrophy after partial denervation: a human case. J Neurol Neurosurg Psychiat 41: 719, 1978.

[2] 2. Brooke MH, Engel WK - The histographic analysis of human muscle biopsies with regard to fibre types: 1. Adult male and female. Neurology 19: 221, 1969.

[3] 3. Brooke MH, Engel WK - The histographic analysis of human muscle biopsies with regard to fibre types: 2. Diseases of the upper and lower motor neuron. Neurology 19: 378, 1969.

[4] 4. Brooke MH, Kaiser KK - Muscie fibre types: how many and what kind? Arch Neurol 23: 369, 1970.

[5] 5. Brooke MH, Kaiser KK - Three «Myosin Adenosine Triphosphatase» systems: the nature of their pH lability and sulphydryl dependence. J Histochem Cytochem 18: 670, 1970.

[6] 6. Buller AJ, Pope R - Plasticity in mammalian skeletal muscle. Philos Soc London (Biol) 278: 295, 1977.

[7] 7. Castaigne P, Laplane D, Fardeau M, Dordain G, Autret A, Hirt L - Myopathie avec anomalies mitochondriales localisées aux fibres de type 1: documents cliniques, histo-chimiques et ultrastructuraux concernant une forme atrophique diffuse à debut oculaire. Rev Neurol 126: 81, 1972.

[8] 8. Dubowitz V, Brooke MH - Muscle Biopsy: a Modern Approach. Saunders, Philadelphia, 1973.

[9] 9. Engel WK - «Ragged-red fibres» in ophthalmoplegia syndromes and their differential diagnosis. In: Abstracts of the Second International Congress on Muscle Diseases. Excerpta Medica, Amsterdam, 1971, pg 28.

[10] 10. Engel WK, Cunninghan CG - Rapid examination of muscle tissue: an improved trichrome method for rapid diagnosis of muscle biopsy fresh frozen section. Neurology 13: 919, 1963.

[11] 11. Jansson E, Syodin B, Tesch P - Changes in muscle fibre type distribution in man after physical training. Acta Physiol Scand 104: 235, 1978.

[12] 12. Lambert CD - Uniform muscle histochemistry: a clinical and biopsy study. Trans Am Neurol Assoc 99: 57. 1974.

[13] 13. Lömo T - The role of activity in the control of membrane and contractile properties of skeletal muscle. In: Thesleff S (ed): Motor Innervation of Muscle. Academic Press, New York, 1976, pg 289.

[14] 14. Maunder-Sewry CA, Dubowitz V. - Needle muscle biopsy for carrier detection in Duchenne muscular dystrophy: 1. Light microscopy, histology, histochemistry and quantitation. J Neurol Sci 305, 1981.

[15] 15. Morgan-Hughes JA, Mair WGP - Atypical muscle mitochondria in oculoskeletal myopathy. Brain 96: 215, 1973.

[16] 16. Munsat TL, McNeal D, Waters R - Effects of nerve stimulation of human muscle. Arch Neurol 33: 608, 1976.

[17] 17. Nachlas MM, Tsou KC, de Souza E, Cheng CS, Seligman AM - Cytochemical demonstration of succinic dehydrogenase by the use of a new p-nitrophenyl substituted dite-trazole. J Histochem Cytochem 5: 420, 1957.

[18] 18. Novikoff AB, Shin MY, Drucker J - Mitochondrial localization of oxidative enzymes: staining results with two tetrazolium salts. J Biophys Biochem Cytol 9: 47, 1961.

[19] 19. Olson W, Engel WK, Walsh GO, Einaugler R - Oculocraniosomatic neuromuscular disease with «ragged-red» fibres: histochemical and ultrastructural changes in limb muscles of a group of patients with idiopathic progressive external ophthalmoplegia. Arch Neurol 26: 193, 1972.

[20] 20. Wattenberg LW, Leong JL - Effects of coenzyme Q₁₀ and menadione succinic dehydrogenase activity as measured by tetrazolium salt reduction. J Histochem Cytochem 8: 296, 1960.