Peripheral neuropathy of metachromatic leucodystrophy: observations on segmental demyelination and remyelination and the intracellular distribution of sulphatide.

Abstract

Peripheral nerve abnormalities in metachromatic leucodystrophy have been noted many times since Jacobi (1947) first reported metachromatic material in the sciatic nerve of her patient. The finding of metachromatic granules in a peripheral nerve biopsy, usually the sural nerve, has been recommended as a method of diagnosing this disease (Thieffry and Lyon, 1959;Hagberg, Sourander, and Thoren, 1962). The occurence of granules, mainly in Schwann cells, and also in macrophages, has been thought to be due to the same metabolic anomaly affecting the cells responsible for myelin formation: oligodendroglia in the central nervous system, and Schwann cells in the peripheral nervous system. Phase-contrast and electron microscope studies (Webster, 1962) and electrophysiological observations (Fullerton, 1964) NERVE TEASING This was done by a method modified from Thomas's (1955) account. Formalin-fixed nerves were washed in water and placed in 1 % aqueous osmic acid for 24 hours. After further washing, they were placed in 60 % glycerol in water until required. Under a dissecting microscope, at a magnification of x 25 or x 50, single nerve fibres were teased out freehand from fascicles, using fine sewing needles for dissection. Individual fibres were placed on clean slides in batches of about 20, straightened, dried in air at 37'C., and mounted in glycerine jelly. Some specimens of nerves after fixation were stained in bulk by the Hirsch-Peiffer method, by immersion in acidified cresyl violet for 24 hours, and then macerated in 60 % glycerine before being teased.

Peripheral neuropathy detected on electrophysiological study as first manifestation of metachromatic leucodystrophy in infancy.

“…The deposit of metachromatic granules in the Schwann cells suggests that this is the cause of the nerve demyelination seen in biopsies (Dayan, 1967;Aziz and Pearce, 1968;Olsson and Sourander, 1969) and the myelin degeneration accounts for the marked reduction of motor nerve conduction velocity. In our patient there was a good correlation with the severe demyelination observed in nerve fibres on biopsy of muscle and nerve (Figs 1 and 2).…”

“…The electrophysiological alterations are paralleled by the structural changes consisting of segmental demyelination observed in nerve biopsy (Dayan, 1967;Aziz and Pearce, 1968). Since the first findings of metachromatic substance in the nerve (Thieffry and Lyon, 1959), sural nerve biopsy has proved to be the most appropriate method for the diagnosis of metachromatic (Accepted 14 August 1974.…”

Globular neuropathy. A disorder of axons and Schwann cells.

“…For light microscopy they were fixed in buffered formol saline and paraffin and frozen sections cut and stained by conventional methods. Isolated fibres were 'teased' from the nerve by freehand dissection after post-fixation in 10% osmic acid and maceration in 60% glycerine (Dayan, 1967). The internodal lengths and diameters of such fibres were measured directly with a micrometer eyepiece at magnifications of x 100 and x 950 respectively.…”

“…Axonal degeneration or segmental demyelination (or both) may occur and their histological appearances are now well known. Disorders associated with primary destruction of axis cylinders include the classical example of Wallerian degeneration, and the latter, sometimes termed 'Schwann cell diseases', includes the neuropathies of diabetes mellitus and metachromatic leucodystrophy (Dayan, 1967).…”

Metachromatic Leukodystrophy: A Comparative Study of the Ultrastructural Findings in the Peripheral Nervous System of Three Cases, One of the Late Infantile, One of the Juvenile and one of the Adult Form of the Disease

“…In as far as it affects the peripheral nervous system, the deficiency leads on the one hand to storage of metachromatic material consisting of sulfatides (galactosyl-and lactosylsulfatides), in lysosomes of Schwann cells and macrophages, on the other hand to a segmental demyelination Dayan (1967). This demyelination is probably caused by an increase of sulfatides and a concomitant decrease of cerebrosides in the myelin sheaths.…”