Treatment The only preventive treatment for diabetic neuropathy is the maintenance of blood glucose concentration at close to normal range. The prevailing view, derived from long-term human studies, is that there is a relationship between peripheral nerve damage and inadequate regulation of the diabetes. This is supported by the findings of the National Diabetic Complications Trial, in which 715 patients with type 1 diabetes were followed for 6 to 10 years. There was a relation between strict glucose control by means of an intravenous insulin infusion system and a reduction or delay in the occurrence of painful neuropathic symptoms, retinopathy, and nephropathy. However, this came at the price of a threefold increase in hypoglycemic reactions (see also Samanta and Burden). Whether similar protective effects of glucose control apply to type 2 diabetes is not known, but for most patients rigid control is impractical. A number of small trials have been conducted with aldose reductase inhibitors based on theoretical considerations of the above-discussed metabolic changes. Some recent interest has also been directed at the therapeutic use of gangliosides, which are normal components of neuronal membranes and can be administered exogenously. These approaches have not entered routine practice.
Treatment using gene transfer had been pursued by our group. In experimental models of diabetic neuropathy, the intramuscular administration of VEGF has had a beneficial effect on several measures of nerve conduction and on the histologic changes of diabetic nerve damage in the treated limb (Ropper et al, 2009). Whether this was mediated by a trophic influence on nerves and Schwann cells, or is the result of angiogenesis, is not known. With similar intentions, two trials of NGF injections in almost 500 patients conducted by Apfel and colleagues gave equivocal results, the first being positive and the followup study not showing improvement. VEGF has resulted in improvement of sensory symptoms but not of nerve conduction or of the sensory examination in a trial we conducted.
The distressing paresthesias of the distal extremities can be managed with amitriptyline, other tricyclic antidepressants, or one of the newer generation of antidepressants, duloxitine, gabapentin, or pregablain but the response is usually incomplete. Shooting, stabbing pain also responds to some degree to anticonvulsant drugs but only modest effects can be expected. Gabapentin may give reasonable results, perhaps in part because high doses are tolerated (Gorson et al, 1999). Topical creams with capsaicin, lidocaine or other substances, or compounds with several of these (including ketorolac, gabapentin, ketamine) have been found helpful by a few patients but do not have support in randomized trials. Nerve blocks and epidural injections have been helpful in very few patients. In the proximal asymmetrical, truncal, or ophthalmoplegic neuropathies, the severe pain usually lasts for only a short period and requires the judicious use of analgesics, as outlined in Chap. 7. The course in patients with the distal, symmetrical sensory neuropathy is generally of slow progression, but in the other types improvement and eventual recovery may be expected over a period of months or years.
ASYMMETRICAL AND MULTIFOCAL POLYNEUROPATHIES (MONONEUROPATHY, OR MONONEURITIS MULTIPLEX) (TABLE 43-4)