The pathology of neuropathies with focal thickening of the myelin sheath (tomaculous neuropathy): Studies on the formation of the abnormal myelin sheath

Abstract

The sural nerves of 4 patients showed similar pathological features of sausage-shaped thickenings of the myelin sheaths ranging in length from 80 to 250 μm, of up to 27 μm diameter and affecting fibres of all sizes. From 25 to 82% of internodes in the different cases showed these thickenings, which were both in the paranodal and internodal areas. Segmental demyelination with remyelination and early onion-bulb formation were also features of the affected nerves. The term “tomaculous neuropathy” ( tomaculum, Latin = sausage) is proposed for this pathological condition. Study of the ultrastructure of these sausage-shaped thickenings and of the apparently normal areas of the myelin sheaths demonstrated various abnormalities which may have led to the formation of the thickenings: 1. (1) Hypermyelination with an excessive number of myelin lamellae for the axonal circumference. Observed values of the ratio (number of lamellae) : (axonal circumference in μm) were up to 73.5, while normal values were from 4.25 to 7.25. 2. (2) Redundant loop formation, with a surplus loop of the myelin sheath secondarily wrapping around the original myelin sheath. The structure of some of these loops was extremely complex. 3. (3) Branching and duplication of the mesaxon, leading to an increase in the number of myelin lamellae. 4. (4) Transnodal myelination, with spread of the myelin sheath of 1 internode into the region of the next internode. This completely obliterated many nodes of Ranvier whose sites could only be detected by the electron-microscopic demonstration of Schwann cell interdigitating pseudopodia and blind-ending myelin loops. 5. (5) The participation of 2 or more Schwann cells in the formation of 1 myelin sheath. 6. (6) The degeneration of myelin in the adaxonal and/or intramyelin regions between an outer intact layer of the myelin sheath, and the axon. Changes (1), (2), (4) and (6) appeared to be responsible for most of the sausage-shaped thickenings, redundant loop formation being the commonest. Axonal constriction of marked degree was seen within many of the sausage-shaped thickenings. This study indicates that, in pathological conditions of the myelin sheath and/or Schwann cell, the formation of the myelin sheath both during original myelinogenesis and during remyelination after segmental demyelination may be different from the generally accepted normal regular helical construction. Tomaculous neuropathy can occur in a number of different diseases of the peripheral nerves. The clinical picture of the 4 cases described here differed considerably. Two women had familial recurrent brachial plexus neuropathy, 1 patient had recurrent pressure-sensitive neuropathy, and the last patient had a chronic distal sensorimotor neuropathy affecting predominantly the upper limbs. The underlying biochemical or biophysical abnormality of the myelin or Schwann cell leading to the sausage-shaped thickenings of the myelin sheath has not been elucidated.