This disorder gives rise to asymmetrical multiple mononeuropathy indistinguishable from the other angiopathic neuropathies described earlier and, probably based on the same mechanism, mononeuropathies of the lower cranial nerves directly as they exit the skull and pass through the retropharyngeal tissues. The frequency of peripheral nerve involvement in Wegener disease is much lower than in the other of classic vasculitides and the affected vessels are of a smaller caliber than in polyarteritis nodosa. Nonetheless, DeGroot and colleagues emphasized in a prospective analysis of 128 patients with Wegener disease that 25 had evidence of mononeuritis multiplex, with the peroneal nerve most often involved, and an even greater number had distal polyneuropathy; however, the proportion of their cases in which neuropathy was the presenting or sole manifestation of disease was higher than in other series. The finding of circulating c-ANCA is relatively specific for Wegener granulomatosis and for Churg-Strauss disease, as mentioned earlier (Specks et al), and helps to differentiate it from polyarteritis (which may be associated with p-ANCA) and from retropharyngeal carcinoma, chordoma, sarcoidosis, and herpes zoster. Wegener vasculitis as it affects the lower cranial nerves is discussed in Chap. 44.
Treatment is along the lines of corticosteroids and rituximab or cyclophosphamide as already discussed.
This process may be associated with a vasculitic mononeuritis multiplex as well as a more generalized polyneuropathy. In many cases, glomerulonephritis, arthralgia, and purpura are conjoined, reflecting the systemic nature of the vasculopathy, but the mononeuritis may occur in isolation. The evolution in the cases under our care has been slower than in the typical vasculitic neuropathies, sometimes taking weeks or months between attacks of mononeuropathy. The neurologic disorder may become quiescent for long periods, during which time considerable improvement may occur. There is no evident relationship between the mode of onset or severity of the neuropathy and the concentration of cryoprecipitable proteins in the serum. These proteins can be detected by cooling the serum and demonstrating a precipitation of IgG and IgM proteins that redissolve upon warming to 37°C (98.6°F). To demonstrate this phenomenon the blood sample must be carefully transported to the laboratory in a warm water bath. An association of cryoglobulinemia with hepatitis C is well known, but many patients have had polyneuropathy from cryoglobulins but without the infection.
Treatment Garcia-Bragado and colleagues suggested that the neuropathy can be stabilized by corticosteroids and cyclophosphamide, but rituximab has been increasingly employed rather than cyclophosphamide and plasma exchange; the comparison between approaches has not been systematically tested. If the underlying problem is hepatitis C infection, pegylated alpha-interferon and ribavirin are usually administered as antiviral agents, with rituximab if the neuropathy is severe. It is too early to judge if the new protease inhibitors for the treatment of hepatitis C will reduce the occurrence and degree of polyneuropathy. Other aspects of the condition are discussed further under “Polyneuropathy Associated with Paraproteinemia” and “Other Vasculitic Neuropathies.”