Pathological Study of the Sural Nerve in Fabry’s Disease

Abstract

A man with Fabry''s disease, who died at 52, suffered from lancinating limb pains between the age of 20-27, and from severe arthalgia between 20-40. The sural nerve showed a severe loss of fibers (16,814 myelinated fibers/mm2), chiefly affecting the small myelinated fibers. Inclusions of both homogeneous and lamellated appearance were present in the perineurial cells, fibroblasts and vessel walls. Teased fibers displayed moderate remyelination, regeneration and the presence of globular focal myelin thickening. The transient time course of painful manifestations in this case is stressed in view of a possible pathogenesis of pain in Fabry''s disease. It appears that small-fiber neuropathy is not directly related to the occurrence of pain symptoms, since the prevalent loss of small myelinated fibers was seen in the absence of actual pain. The small sensory neurons in the dorsal root ganglia, that are especially affected by lipid accumulation, probably give rise to abnormal discharges; this produces pain via the prevalence of the small-fiber vs. the large-fiber input to the dorsal horn of the spinal cord (gate control theory). Pain fits may spontaneously abate if degeneration and loss of the small sensory neurons overstep a critical level.