ABSTRACT
A relationship between peripheral neuropathy and plasma cell dyscrasias was described early in the 20th century,1-3 and in the last decade or so numerous studies have firmly established a link between these conditions. Monoclonal proteins are now known to be present in a sizable group of patients who were formerly thought to have idiopathic neuropathy.4 The immunoglobulins can be detected in the serum or urine by immunoelectrophoresis or by the more sensitive immunofixation test. While the majority of patients with monoclonal gammopathy have a monoclonal protein of undetermined significance (MGUS), approximately one-third have, or ultimately develop, a malignant disorder such as myeloma or its osteosclerotic variant (POEMS syndrome, described below), Waldenström’s macroglobulinemia, amyloidosis, cryoglobulinemia, or lymphoma. In certain conditions (e.g. osteosclerotic myeloma, amyloidosis, and MGUS) neuropathy may be the initial manifestation of the disease (Table 12.1).5-10
The prevalence of monoclonal gammopathy in the general population is 1-3%, and therefore a direct pathophysiologic relationship between
uncertain but several lines of evidence suggest that there is a causal connection. Epidemiologic data indicate that the prevalence of MGUS is higher in patients with idiopathic neuropathy than in those with a known cause,4 and the prevalence of neuropathy is manifestly higher in patients with monoclonal gammopathy than in the general population.11 Furthermore, under some circumstances a demyelinating neuropathy can be induced in animals by transfer of serum and by intraneural injection from patients with MGUS neuropathy.12-14 The pivotal pieces of evidence, however, are the findings of specific anti-nerve autoantibodies in the serum of certain patients with paraproteinemic neuropathy,15-18 the immunofluorescent staining of the responsible immunoglobulin in the endoneurium,15-19 and improvement of the neuropathy in some cases by immunomodulating therapies, all implicating the protein as the proximate cause of nerve damage.6,20-25
As a prelude to understanding these conditions, a brief review of the cardinal features of peripheral nerve disease is necessary. Neuropathy may be classified into broad categories according to the clinical manifestations and the type of nerve fiber that is affected
Neuropathy in plasma cell disorders Kenneth C Gorson, Allan H Ropper
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