Skip to main content
SpringerLink
Log in

Morphological study of peripheral nerve changes induced by chloroquine treatment

  • Regular Papers
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

Nerve biopsies were performed in four patients with suspected chloroquine induced neuromyopathy. Three of the patients were treated with high doses of chloroquine for connective tissue disease, while one patient was taking this drug as malaria prophylaxis. Morphological studies demonstrated the presence of segmental demyelination and remyelination in all cases. Cytoplasmic inclusions were observed in Schwann cells, in perineurial and endothelial cells, and in some interstitial cells. They were never observed within axons. Occasional curvilinear profiles were seen in perineurial and Schwann cells. Perineurial calcifications were observed in two cases. The results of this morphological study suggest that chloroquine neuropathy is essentially due primary involvement of Schwann cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Carpenter S, Karpati G, Andermann F, Jacob JC, Andermann E (1977) The ultrastructural characteristics of the abnormal cytosomes in Battens-Kufs' disease. Brain 100:137–156

    Google Scholar 

  2. Fardeau M (1973) Normal ultrastructural aspect of human motor end-plate and its pathologic modifications. In: Pearson CM, Mostofi FK (eds) The striated muscle. Williams and Wilkins. Baltimore, pp 342–363

    Google Scholar 

  3. Fardeau M (1973) Caractéristiques cytochimiques et ultrastructurales des différents types de fibres musculaires squelettiques extra-fusales (chez l'homme et quelques mammifères). Ann Anat Pathol 18:7–34

    Google Scholar 

  4. Fardeau M, Engel WK (1969) Ultrastructural study of a peripheral nerve biopsy in Refsum's disease. J Neuropathol Exp Neurol 28:278–294

    Google Scholar 

  5. Fardeau M, Tomé FMS, Simon P (1979) Muscle and nerve changes induced by perhexiline maleate in man and mice. Muscle Nerve 2:24–36

    Google Scholar 

  6. Frisch W, Lüllmann-Rauch R (1979) Differential effects of chloroquine and of several other amphiphilic cationic drugs upon rat choroid plexus. Acta Neuropathol (Berl) 46:203–208

    Google Scholar 

  7. Fukuhara N, Tsubaki T (1970) Chloroquine neuropathy: an electron microscopic study on the skeletal muscle and peripheral nerve (in Japanese). Clin Neurol (Tokyo) 10:337–346

    Google Scholar 

  8. Garcin R, Rondot P, Fardeau M (1964) Sur les accidents neuromusculaires et en particulier sur une “myopathie vacuolaire” observés au cours d'un traitement prolongé par la chloroquine. Rev Neurol (Paris) 111:177–195

    Google Scholar 

  9. Gérard JM, Stoupel N, Collier A, Flament-Durand J (1973) Morphologic study of a neuromyopathy caused by prolonged chloroquine treatment. Eur Neurol 9:363–379

    Google Scholar 

  10. Godeau P, Herreman G, Himmich H, Godet-Guillain J, Chevallay M, Fardeau M (1976) Neuromyopathie due à la chloroquine au cours du lupus érythematémateux: deux nouvelles observations soulignant la nécessité de l'étude ultrastructurale de la biopsie musculaire. Ann Méd Interne (Paris) 127:544–551

    Google Scholar 

  11. Gumbinas M, Larsen M, Lin HM (1975) Peripheral neuropathy in classic Nieman-Pick disease: ultrastructure of nerves and skeletal muscles. Neurology 25:107–113

    Google Scholar 

  12. Humphrey JG, Rewcastle NB (1963) Vacuolar myopathy. A clinical and electron microscopic study. Trans Am Neurol Assoc 88:225–226

    Google Scholar 

  13. Ivy GO, Schottler F, Wenzel J, Baudry M, Lynch G (1984) Inhibitors of lysosomal enzymes: aceumulation of lipofuscin-like dense bodies in the brain. Science 226:985–987

    Google Scholar 

  14. Jacobs JM, Costa-Jussa FR (1985) The pathology of amiodarone neurotoxicity. II. Peripheral neuropathy in man. Brain 108:753–769

    Google Scholar 

  15. Jones CJP, Salisbury RS, Jayson MIV (1984) The presence of abnormal lysosomes in lymphocytes and neutrophils during chloroquine therapy: a quantitative study. Ann Rheum Dis 43:710–714

    Google Scholar 

  16. Klinghardt GW (1977) Neuronal storage dystrophy in chronic chloroquine intoxication. In: Riozin L, Shiraki H, Grcevic (eds) Neurotoxicology, Raven Press, New York, pp 371–380

    Google Scholar 

  17. Léger JM, Puifoulloux H, Dancea S, Hauw JJ, Bouche P, Rougemont D, Laplane D (1986) Neuromyopathies à la chloroquine: 4 cas au cours d'une prophylaxie antipaludéenne. Rev Neurol (Paris) 142:746–752

    Google Scholar 

  18. Lhermitte F, Marteau R, Chedru F, Mallecourt J, Estrade G, Godet-Guillain J, Chevallay M (1977) Neuromyopathie à la chloroquine. Nouv Presse Med 6:3205–3207

    Google Scholar 

  19. Lüllmann H, Lüllmann-Rauch R, Wassermann O (1975) Drug-induced phospholipidoses. II. Tissuc distribution of the amphiphilic drug chlorphentermine. CRC Crit Rev Toxicol 4:185–218

    Google Scholar 

  20. MacDonald RD, Engel AG (1970) Experimental chloroquine myopathy. J Neuropathol Exp Neurol 29:479–499

    Google Scholar 

  21. Meier C, Kauer B, Muller U, Ludin HP (1979) Neuromyopathy during chronic amiodarone treatment. A case report. J Neurol 220:231–239

    Google Scholar 

  22. Neville HE, Maudner-Sewry CA, McDougal J, Sewell JR, Dubowitz V (1979) Chloroquine-induced cytosomes with curvilinear profiles in muscle. Muscle Nerve 2:376–381

    Google Scholar 

  23. Pagés M, Pagés AM (1984) Lésions du nerf périphérique dans la neuromyopathie à la chloroquine. Ann Pathol 4:289–295

    Google Scholar 

  24. Schmalbruch H (1980) The early changes in experimental myopathy induced by chloroquine and chlorphentermine. J Neuropathol Exp Neurol 39:65–81

    Google Scholar 

  25. Singh KP, Krause W, David H, Zglinicki TV (1985) Effects of chloroquine on hepatocytic organelles in rat. Exp Pathol 28:119–124

    Google Scholar 

  26. Tomé FMS (1981) Pitfalls in the electron microscopic examination of skeletal muscle. Muscle Nerve 4:76–79

    Google Scholar 

  27. Tomé FMS, Mira JC (1981) Contribution of the morphological techniques to the study of peripheral nerve lesions in man and experimental animals. Int J Microsurg 3:152–160

    Google Scholar 

  28. Tomé FMS, Brunet P, Fardeau M, Hentati F, Reix J (1985) Famílial disorder of the central and peripheral nervous systems with particular cytoplasmic inclusions in peripheral nerves, muscle satellite cells, and blood capillaries. Acta Neuropathol (Berl) 68:209–217

    Google Scholar 

  29. Tomé FMS, Fardeau M, Lenoir G (1977) Ultrastructure of muscle and sensory nerve in Fabry's disease. Acta Neuropathol (Berl) 38:187–194

    Google Scholar 

  30. Van Lis JMJ, Jennekens FGI, Veldman H (1979) Calcium deposits in the perineurium and their relation to lipid accumulation. J Neurol Sci 43:367–375

    Google Scholar 

  31. Whisnant JP, Espinosa RE, Kierland RR, Lambert EH (1963) Chloroquine neuromyopathy. Mayo Clin Proc 38:501–513

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Karolinska Hospital, Stockholm, Sweden

    R. Tegnér

  2. Groupe de Recherches de Biologie et Pathologie Neuromusculaires, INSERM U. 153, 17 rue du Fer-à-Moulin, F-75005, Paris, France

    F. M. S. Tomé & M. Fardeau

  3. Service de Médecine Interne, Hôpital de la Pitié, Paris, France

    P. Godeau

  4. Service de Neurologie et Neuropsychologie, Hôpital de la Salpêtrière, Paris, France

    F. Lhermitte

Authors
  1. R. Tegnér
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. M. S. Tomé
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Godeau
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F. Lhermitte
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Fardeau
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tegnér, R., Tomé, F.M.S., Godeau, P. et al. Morphological study of peripheral nerve changes induced by chloroquine treatment. Acta Neuropathol 75, 253–260 (1988). https://doi.org/10.1007/BF00690533

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00690533

Key words

Search

Navigation