The Diagnostic Yield of a Standardized Approach to Idiopathic Sensory-Predominant Neuropathy

Abstract & Commentary

Synopsis: Patients with sensory-predominant neuropathy should be tested for glucose tolerance and vitamin B12 concentration.

Source: Smith AG, et al. Arch of Intern Med. 2004;164: 1021-1025.

Smith and colleagues report that 61% of patients with idiopathic neuropathy, referred to a tertiary medical center for further evaluation, had an abnormal glucose tolerance test (GTT), with normal HgbA1c or fasting blood glucose in most cases. Of interest, 30% of the patients had normal electrophysiologic studies, although several had skin biopsy showing reduced density of intraepidermal nerve fibers, confirming the diagnosis. Twenty-five percent of patients reported having at least 1 first-degree relative with symptoms of neuropathy, suggesting direct inheritance or familial predisposition, as may be seen in such conditions as celiac disease or diabetes.

B12 deficiency was found in 2 of 87 patients tested. The diagnostic yield of other tests was low, so that they were not recommended. In 31% of patients, no known cause could be identified despite extensive testing.


The paper emphasizes the importance of testing for glucose intolerance in otherwise unexplained neuropathy. The yield for other tests may have been confounded by referral bias. Most of the patients were evaluated elsewhere first, so that only those with negative tests would have been referred for further evaluation. Glucose intolerance was obviously missed, probably because its link to neuropathy is still not widely appreciated. More meaningful recommendations for testing would have to come from studies of newly diagnosed patients, or non-selected neuropathy populations. The fact that approximately one third of patients remained undiagnosed, is a reflection of the abysmal state of the field, and the need for more research. — Norman Latov

Dr. Latov is the Director of the Peripheral Neuropathy Center and the Professor of Neurology and Neuroscience at Weill Medical College at Cornell University.