A sensorimotor paralysis, which evolves over several weeks (subacutely) or more slowly, over many months or a year or two, and involves legs more than arms and distal parts more than proximal should lead to a search for diabetes, occult neoplasia (carcinoma, lymphoma, multiple myeloma, or plasmacytoma), HIV, paraproteinemia (including amyloid neuropathy), systemic autoimmune disease, and CIDP. In our experience, the subacute and chronically evolving demyelinating neuropathies (over months) that have slowed motor conduction velocities, conduction block, and relatively normal needle EMG studies generally turn out to be variants of CIDP, some with a paraproteinemia. Marked weakness and reduced muscle action potential amplitudes in the face of minimal denervation, even if present in only a few nerves, also indicate the presence of focal demyelination. Most of the mixed axonal–demyelinating cases in which one eventually arrives at a diagnosis will also be related to an immune (paraproteinemic) or inflammatory (CIDP) process. In exceptional cases, a neoplastic process may remain hidden for as long as 2 or 3 years after the onset of neuropathy. An environmental toxin, endocrine disorder (except for diabetes), or nutritional cause is seldom identified, despite the frequent attribution of obscure polyneuropathies to such causes. Nonetheless, history of exposure to industrial or hobbyist toxins, sociopathy or psychopathy that would lead to toxin ingestion, or foreign travel should be sought and the evaluation should include testing for heavy metals in obscure cases. Unusual causes of nutritional deficiency such as celiac-sprue and other malabsorption syndromes (Whipple disease, Crohn disease, chronic hepatic disease, and particularly intestinal bypass surgery) have usually been obvious enough when present, so that the experienced clinician rarely overlooks them. Perhaps sprue is able to cause a neuropathy with minimal gastrointestinal symptoms. Vitamin B12 deficiency should be sought in cases of large-fiber neuropathy. A difficult problem is that of an older person with a mild, nonprogressive sensorimotor polyneuropathy in whom there is evidence of mild hypothyroidism, marginally low vitamin B12 and folic acid levels in the blood, a somewhat unbalanced diet, perhaps an excessive alcohol intake, and an abnormal glucose tolerance response. It is easy to propose but hard to prove that any of these factors is relevant. Vitamin replacement should be undertaken nonetheless if no other cause is found.
In the purely or predominantly sensory polyneuropathies not caused by diabetes—some painful, some not, and some with marked ataxia—an association with occult carcinoma, an IgM or other paraproteinemia, primary and familial amyloidosis, or Sjögren syndrome are the primary considerations. The problem of a mild sensory neuropathy in an elderly patient with or without burning feet was discussed earlier. When the symptoms are confined to the feet and legs, hereditary sensory neuropathy must always be considered if the condition is long standing. Intoxications with pyridoxine, metals, and idiosyncratic responses to therapeutic medications account for a few chronic sensory neuropathies. Despite all these considerations, we still regularly encounter patients in whom the cause is not disclosed by any of the available tests. We have watched helplessly as some of these patients were reduced to a bed and wheelchair existence and others suffered from pain until they became dependent on opiates.
Table 43-7 lists the laboratory tests that we have found useful in the investigation of this group of neuropathies, with electrophysiology being most valuable.
Diagnosis of Late Chronic Polyneuropathy