Miyakawa et al.
5 were the first to focus the attention on peripheral nerves in WD. Examining the biopsy of the sural nerve in a case of WD, they demonstrated the loss and the irregular shape of myelinated nerve fibers, suggesting that the pathological changes in peripheral nerves consist of a primary demyelination, and a secondary involvement of the axon. These investigators hypothesized that these changes are due to the disturbances of copper metabolism, affecting the Schwann cells and the myelin sheat.
5 Using electrodiagnostic tests, Leven et al.
7 demonstrated, in three patients affected by WD, the decrease of motor nerve and sensory nerve conduction velocity, and the impairment of the sensory action potentials, indicating the damage of major peripheral nerves. Some years later, Madden et al.
8 studied a case of a 61-year-old man affected by WD. They described small areas of demyelination in the peripheral nerves and, considering nerve conduction findings, they suggested that axonal degeneration was the main pathologic change.
8 Jung et al.
10 reported one case whose initial manifestation of WD was polyneuropathy. This subject presented with impairment of distal nerve conduction and limb electromyography quantification. Nerve biopsy showed destroyed myelin sheath associated with axonal damage. Hyperesthesia of the hands and feet developed one year later. Moreover, progression of the earlier electrophysiological abnormalities was documented, demonstrating worsening of the earlier mild demyelinating features in all examined peripheral nerves with the addition of axonal changes. The long-term electromyographic findings suggested axonal involvement, and the pathological examination confirmed the loss of myelin sheath and axon, suggesting a mixed type peripheral neuropathy.
10 These literature reports were consistent with Schwann cells as primary target in WD. However, a recent study by von Giesen et al.
9 seems to contradict this hypothesis. These investigators, using functional quantitative sensory tests (thermal, pain, and vibratory sensation), detected a dysfunction of unmyelinated warm-specific C fibers in WD and a relative preservation of myelinated A-β fibers.
9 No pathologic examination or morphologic tests were performed by these investigators.