However, one is often confronted by a pattern of subacute or chronic polyradiculopathy and abnormal CSF formula for which extensive examination fails to identify any of the diseases enumerated above. This idiopathic form of polyradiculopathy comes to our attention several times yearly. Some will turn out to have a lymphomatous infiltration at autopsy for which reason we have on occasion asked a neurosurgeon to remove a midlumbar (L2 or L3) motor rootlet for examination. Also particularly difficult diagnostically is a polyradiculopathy that involves the motor roots exclusively or predominantly and is indistinguishable from motor neuron disease except for the absence of widespread denervation or of progressive upper motor neuron signs and differing from the immune motor neuropathies discussed further on by the absence of conduction block.
In these common syndromes, reduced sensation, weakness, muscular atrophy, and loss of tendon reflexes progress over a period of months or years. Within this large category, two groups are distinguished. In the first and less chronic of the two, the neuropathy appears over months or a year or two. Comprising this group are acquired processes such as certain metabolic and immune-mediated polyneuropathies. Paraneoplastic neuropathies may also fall into this category, although they are more often subacute in onset, being almost fully developed in a matter of weeks. Leprous neuritis is the one infectious member of this group and also the one exception to the rule that all chronic neuropathies are more or less symmetrical in pattern. The polyneuropathies that make up the second group are far more chronic than the first, evolving insidiously over many years or decades; these are mainly the genetically determined diseases of the peripheral nervous system caused by specific genetic mutations.
Acquired Forms of Chronic Polyneuropathy
The occurrence of a chronic sensorimotor polyneuropathy in association with an abnormality of serum immunoglobulins is recognized with increasing frequency, but its boundaries are still not well established as will be apparent in the following discussion. The excess blood protein, called a paraprotein or “M-spike,” is usually in the form of a monoclonal immunoglobulin. It may be an isolated abnormality or a by-product of a plasma cell malignancy, specifically multiple myeloma, plasmacytoma, or Waldenström macroglobulinemia. Several lines of evidence suggest that a pathogenetically active antibody against components of myelin or axon is present in at least some of these cases. Special forms of neuropathy are also associated with amyloidosis. Both the acquired and genetic forms of amyloidosis are discussed further on.
Neuropathy with monoclonal gammopathy of undetermined significance (MGUS, benign monoclonal gammopathy) The association of a nonneoplastic IgM monoclonal protein and a neuropathy was first described by Forssman and colleagues and was treated as coincidental until Kahn (1980) established a compelling statistical association between the two conditions. A more direct relationship was established by the finding of antiperipheral nerve antibodies in some patients who had such a protein in their blood. This category of polyneuropathy is associated with a monoclonal or sometimes polyclonal excess of immunoglobulin (IgG, IgM, or IgA, rarely others, mainly with a kappa light chain components; see Kyle and Dyck). These cases are far more common than those caused by a malignant plasma cell disorder. In our experience, monoclonal proteins underlie the largest group of otherwise unexplained neuropathies in adults.