Skip to main content
SpringerLink
Log in

Ultrastructure of peripheral nerve in metachromatic leucodystrophy

  • Original Investigations
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

An electron microscopical study of two consecutive nerve biopsies from a patient with metachromatic leucodystrophy (sulphatide lipidosis) was made. The ultrastructural changes observed consisted of: a) irregular whorls of myelin. The myelin in the whorls showed a thickened, sometimes doubled, intraperiod line, which was barely visible in compact myelin; b) “inclusion bodies” up to 1 μ in diameter in the cytoplasm of Schwann cells. These had a lamellar structure, with stacked membranes 60 Å apart; c) a “loose” pattern of the myelin in some nerve fibers, with loss of the intraperiod line, and d) presence of abnormally dense mitochondria with thickened cristae in Schwann cells. It is suggested that: a) the whorl formation and the ultrastructural abnormalities of the myelin in the whorls may be due to impaired myelin synthesis, and b) that the “inclusion bodies” may represent the accumulation of cerebroside sulfate in micellar aggregates. The “loose” pattern of myelin is considered artifactural until proven otherwise.

Zusammenfassung

Zwei aufeinanderfolgende Nervenbiopsien bei einem Patienten mit metachromatischer Leukodystrophie (Sulfatid-Lipoidose) wurden elektronenoptisch untersucht. Die beobachteten ultrastrukturellen Veränderungen bestehen in: a) unregelmäßigen Wirbelbildungen (whorls), in welchen das Myelin Verdickungen, manchmal Verdopplung des Zwischenstreifens (intraperiod line) aufweist, was im kompakten Myelin kaum sichtbar ist. b) “Einschlußkörperchen” mit einem Durchmesser bis zu1 μ im Cytoplasma der Schwann-Zellen. Diese weisen lamelläre Struktur mit einem Membranabstand von 60 Å auf. c) ein “lockeres” (loose) Myelinmuster mit Verlust des Zwischenstreifens in einigen Nervenfasern und d) Auftreten von abnorm dichten Mitochondrien mit verdicktem Cristae in Schwann-Zellen. Es wird angenommen, daß a) die Wirbelbildungen und die ultrastrukturellen Myelinabnormitäten in den Wirbeln einer gestörten Myelinsynthese entsprechen und b) daß die “Einschlußkörperchen” die Anhäufung von Cerebrosidsulfat in micellaren Verbänden darstellen. Das “lockere” Myelinmuster wird vorläufig als artifiziell angesehen.

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

  • Austin, J. H.: Metachromatic form of diffuse cerebral sclerosis. 2. Diagnosis during life by isolation of metachromatic lipids from urine. Neurology (Minneap.)7, 716 (1957).

    Google Scholar 

  • —: Metachromatic sulphatides in cerebral white matter and kidney. Proc. Soc. exp. Biol. (N.Y.)100, 361 (1959).

    Google Scholar 

  • —: Metachromatic form of diffuse cerebral sclerosis. III. Significance of sulphatide and other lipid abnormalities in white matter and kindey. Neurology (Minneap.)10, 470 (1960).

    Google Scholar 

  • Aurebeck, G., K. Osterberg, M. Blaw, S. Chou, andE. Nelson: Electron microscopic observations on metachromatic leucodystrophy. Arch. Neurol. (Chic.)11, 273 (1964).

    Google Scholar 

  • Bargeton, E.: The metachromatic form of leucodystrophy and its relationship to lipidoses and demyelination in other metabolic disorders. In: Brain lipids and lipoproteins and the leucodystrophies, pp 90–103.Folchi-Pr, J. andH. Bauer (Eds.). Amsterdam: Elsevier Publ. Co. 1963.

    Google Scholar 

  • Bertrand, I., S. Thieffrey, andE. Bargeton: Leucodystrophie Familiale et determination Spleno-Hepatique Characterisant un Trouble Général du Metabolisme. Rev. neurol.91, 161 (1954).

    Google Scholar 

  • Brain, W. R., andJ. G. Greenfield: Late infantile metachromatic leukoencephalopathy with primary degeneration of interfascicular oligodendroglia. Brain72, 291 (1950).

    Google Scholar 

  • Cravioto, H.: The role of Schwann cells in the development of human peripheral nerves. J. Ultrastruct. Res.12, 634 (1965).

    Google Scholar 

  • Einarson, L., andA. V. Neel: Contribution to the study of diffuse brain sclerosis with a comprehensive review of the problem in general and a report of two cases. Acta Jutlandica14, 1 (1942).

    Google Scholar 

  • Feigin, I.: Diffuse cerebral sclerosis (metachromatic leukoencephalopathy Amer. J. Path.30, 715 (1954).

    Google Scholar 

  • Geren, B. B.: The formation from the Schwann cell surface of myelin in the peripheral nerves of chick embryos. Exp. Cell Res.7, 558 (1954).

    Google Scholar 

  • Greenfield, J. G.: A form of progressive cerebral sclerosis in infants associated with primary degeneration of interfascicular glia. J. Neurol. Psychopath.13, 289 (1933).

    Google Scholar 

  • Gruner, J. R.: Le Biopsie Nerveuse en Microscopie Electronique. C.R. Soc. Biol. (Paris)1954, 1963 (1960).

    Google Scholar 

  • Hagberg, B., P. Sourander, L. Svennerholm, andH. Voss: Late infantile metachromatic leucodystrophy of the genetic type. Acta paediat. (Uppsala)49, 135 (1960).

    Google Scholar 

  • Hagberg, B., P., Sourander andL. Thoren: Peripheral nerve changes in the diagnosis of metachromatic leucodystrophy. Acta paediat. (Uppsala)135 Suppl. 63, (1962).

  • Hess, R., andW. Stäubli: The development of aortic lipidosis in the rat. A correlative histochemical and electron microscopic study. Amer. J. Path.43, 301 (1963).

    Google Scholar 

  • Hirsch, Th. V., u.J. Peiffer: Über histologische Methoden in der Differentialdiagnose von Leukodystrophien und Lipoidosen. Arch. Psychiat. Neurol.194, 88 (1955).

    Google Scholar 

  • Holländer, H.: A staining method for cerebroside sulfuric-esters in brain tissue. J. Histochem. Cytochem.11, 118 (1963).

    Google Scholar 

  • Jatzkewitz, H.: Zwei Typen von Cerebrosidschwefelsäureestern als sog. “Prälipoide” und Speichersubstanzen bei der Leukodystrophie Typ Scholz (Metachromatischen Form der diffusen Sklerose). Hoppe-Seylers Z. physiol. Chem.311, 279 (1958).

    Google Scholar 

  • —: The role of cerebroside sulphuric esters in leucodystrophy and a new method for the quantitative ultramicro-determination of the brain sphingolipids In: Brain lipids and lipoproteins and the leucodystrophies, pp. 147–152.Folch-Pi, J. andH. Bauer (Eds.). Amsterdam: Elsevier Publ. Co. 1963.

    Google Scholar 

  • Lazarus, S. S., B. J. Wallace, andB. W. Volk: Neuronal enzyme alterations in Tay-Sachs disease. Amer. J. Path.41, 591 (1962).

    Google Scholar 

  • Lynn, R., andR. D. Terry: Lipid histochemistry and electron microscopy in adult Niemann-Pick disease. Amer. J. Med.37, 987 (1964).

    Google Scholar 

  • Norman, R. M.: Diffuse progressive metachromatic leucoencephalopathy; a form of Schilder's disease related to the lipidoses. Brain70, 234 (1947).

    Google Scholar 

  • O'Brien, J. S.: A molecular defect of myelination. Biochem. biophys. Res. Commun.15, 484 (1964).

    Google Scholar 

  • —: Stability of the myelin membrane. Science147, 1099 (1965).

    Google Scholar 

  • —M. D. Stern, B. H. Landing, J. K. O'Brien, andG. N. Donnell Generalized gangliosidosis. Another inborn error of ganglioside metabolism Amer. J. Dis. Child.109, 338 (1965).

    Google Scholar 

  • Scholz, W.: Klinische, pathologisch-anatomische und erbbiologische Untersuchungen bei familiärer, diffuser Hirnsklerose im Kindesalter. Z. ges. Neurol. Psychia.99, 651 (1925).

    Google Scholar 

  • Svennerholm, L.: Some aspects of the biochemical changes in leucodystrophy. In: Brain lipids and lipoproteins and the leucodystrophies, pp. 104–119.Folch-Pi J., andH. Bauer (Eds.). Amsterdam: Elsevier Publ. Co. 1963.

    Google Scholar 

  • Terry, R. D., K. Suzuki, andM. Weiss: Biopsy studies in 3 cases of metachromatic leucodystrophy. Presented before the 41st Annual Meeting of the Amer. Assn. Neuropath., Atlantic City N. J., June 13, 1965. J. Neuropath. exp. Neurol.25, 141–143 (1966).

    Google Scholar 

  • —, andM. Weiss: Studies in Tay-Sachs disease. II. Ultrastructure of the cerebrum. J. Neuropath. exp. Neurol.22, 18 (1963).

    Google Scholar 

  • Thieffrey, S., etG. Lyon: Diagnostic d'un cas de Leucodystrophie Metachromatique (Typ Scholz) par la Biopsie d'un nerf Péripheric. Rev. neurol.100, 452 (1959).

    Google Scholar 

  • Vandenheuvel, F. A.: Structural studies of biological membranes: The structure of myelin. Ann. N.Y. Acad. Sci.122, 57 (1965).

    Google Scholar 

  • Webster, H. DeF: Schwann cell alterations in metachromatic leucodystrophy. Preliminary phase and electron microscopic observations. J. Neuropath. exp. Neurol.21, 534 (1962).

    Google Scholar 

  • —,D. Spiro, B. Waksman, andR. D. Adams: Phase and electron microscopic studies of experimental diphtheritic neuritis. J. Neuropath. exp. Neurol.20, 34 (1961).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The sections of Neuropathology, Chemical Pathology, and Pediatric Pathology of the University of Southern California School of Medicine, 1200 North State Street, P.O.Box 134, 90033, Los Angeles, California, USA

    Humberto Cravioto, John S. O'Brien, Benjamin H. Landing & Barbara Finck

  2. Children's Hospital of Los Angeles, 1200 North State Street, P.O.Box 134, 90033, Los Angeles, California, USA

    Humberto Cravioto, John S. O'Brien, Benjamin H. Landing & Barbara Finck

Authors
  1. Humberto Cravioto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John S. O'Brien
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Benjamin H. Landing
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Barbara Finck
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This investigation was supported in part by Public Health Service Research Grant No. FR-86 from the N.I.H. Division of Research Facilities and Resources.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cravioto, H., O'Brien, J.S., Landing, B.H. et al. Ultrastructure of peripheral nerve in metachromatic leucodystrophy. Acta Neuropathol 7, 111–124 (1966). https://doi.org/10.1007/BF00686778

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00686778

Keywords

Search

Navigation