Commentary by Judith Brenner MD, Associate Program Director, NYU Internal Medicine Residency Program
Diabetic neuropathy is one of the most commonly encountered complications of diabetes mellitus. It is seen in up to 20% of diabetics. Patients typically present with neuropathic pain in a “glove and stocking” distribution with the earliest signs in the feet. Night time complaints of “my feet are on fire” are common. Relying on a patient’s complaint of “pain” or “numbness” is inadequate in the diagnosis of peripheral neuropathy since almost half of patients with ulceration lack these complaints.
To briefly review, physical examination centers on assessment of vibration since it is often one of the earliest neurological signs. A 128-Hz tuning fork is applied to the bony prominence on the dorsal aspect of the first toe just proximal to the nail bed, over the interphalangeal joint. The patient is asked what he or she feels. If impairment exists at this distal bony prominence, the examiner can proceed to test more proximal prominences (such as the malleollus, patella, etc) to assess the extent. Testing the Achilles reflex is also useful. In Sapira’s text, “Art and Science of Bedside Diagnosis”, 15% of patients lack an Achilles reflex. Of those 15%, almost 80% have diabetes. The best technique for eliciting the reflex requires that the patient sit comfortably with legs dangling over the table. The examiner dorsiflexes the ankle and then taps the tendon. Dorsiflexion adds tone to the system, thus accentuating the reflex.
Today, the monofilament test is used most often because of its operating characteristics. It has been found that the inability to sense the monofilament is predictive of ulceration (LR of 2.9). Conversely, the presence of sensation argues against subsequent amputation.
As for treatment, it was first shown in DCCT in 1993(1) that intensive insulin therapy in type I DM reduced the risk of developing clinical neuropathy by 61%. The treatment goal is to slow the progression of neuropathy rather than to overcome pain. Beyond glucose control, treatment has traditionally included antidepressants and anticonvulsants. In a recent systematic review, Wong et al (2) investigated the analgesic efficacy of several different classes of analgesics in managing neuropathy. Studies included in this review included adult patients over 18 years of age who were treated with oral or topical analgesics for short periods of time (2 weeks- 6 months). The drugs investigated included antidepressants (TCAs and SSRIs), opioids, tramadol, capsaicin, anticonvulsants, and NMDA antagonists. In each study, the investigated drug was compared to a placebo. The primary outcome that the investigators were interested in was a 50% reduction of pain, which translated into a “moderate” improvement in global pain. The secondary outcome was the number of patients who withdrew secondary to adverse events.
The most dramatic results were in the classes of tricyclic antidepressants (amitriptyline, desipramine and imipramine) where the pooled odds ratio of the primary outcome (50% reduction of pain) was 22.24. More simply, the odds of a 50% reduction in pain in the treatment group was 22.24 times more likely that in the placebo group. The pooled odds ratio of the secondary outcome (number of patients who withdrew from adverse events) was 2.32. The most common adverse events were dry mouth and sedation.
Other drugs that had favorable findings included traditional anticonvulsants (sodium valproate, carbamazepine) with a pooled odds ratio of treatment efficacy of 5.33 and withdrawal secondary to adverse events, 1.51. In comparison, the pooled odds ratio of treatment efficacy with newer anticonvulsants (including gabapentin) was 3.25, but the ratio of withdrawal secondary to adverse events was 2.98. In other words, the odds of someone achieving a “moderate improvement in global pain” was only slightly more likely than needing to withdraw secondary to an adverse event. Of the remaining drugs studied, the efficacy compared with likelihood of withdrawal in descending order is as follows: opioids, newer generation anticonvulsants and lastly, capsaicin.
1. DCCT: The effect of intensive treatment of diabetes on the development and progression of long-term complications in IDDM. NEJM 329:977-986, 1993.