Presentation, Diagnosis, and Classification of Diabetic Neuropathy in Older Adults
D.A. Greene, MD

This article was adapted from a session at the 1999 American Geriatrics Society Annual Meeting.

Diabetic neuropathy is the most common neuropathy in developed nations. It accounts for more hospitalizations than all of the other diabetes-associated complications combined and is responsible for the vast majority of amputations in patients with diabetes. Prevalence estimates vary depending on the diagnostic criteria used: it can affect up to 70% of people with diabetes; in population-based studies, the figure is probably about two-thirds. Studies in different countries yield prevalences that range from one-quarter to two-thirds of the patients with diabetes.

Diabetic neuropathy is related to the duration of diabetes. In most cases, it is also related to the degree of diabetic control, with a higher hemoglobin A1c level being associated with a higher prevalence of diabetic neuropathy. In clinical studies that have looked at the complications of diabetes, there has been adequate representation of people with diabetic neuropathy. About 40% of the subjects in the Diabetes Control and Complications Trial had at least one finding of diabetic neuropathy, and in several cross-sectional studies reported from Europe a significant portion of the people had clinical manifestations of diabetic neuropathy.

Definition and Classification The definition of diabetic neuropathy is problematic. In contrast to the other complications of diabetes, diabetic neuropathy is actually a set of distinct clinical syndromes. These syndromes involve different regions of the peripheral nervous system and may occur singly or in combination. The diagnosis of diabetic neuropathy is as problematic as its definition; it is a clinical diagnosis of exclusion. There are characteristic findings, but they are not pathognomonic, and so other causes must be excluded by appropriate clinical and laboratory evaluation.

As stated, diabetic neuropathy can be classified into several distinct clinical syndromes, each with a characteristic set of signs and symptoms. The clinical findings reflect the injured component of the peripheral nervous system. One type is distal symmetric polyneuropathy, and another is focal neuropathy. If the femoral nerve is involved, the condition is called either femoral neuropathy or lumbosacral plexopathy. There can be involvement of truncal nerves, with diabetes producing truncal neuropathies. There are also a variety of individual mononeuropathies, where the signs and symptoms are limited to the distribution of a single nerve; these neuropathies usually occur as the result of pressure palsies.

Distal Symmetric Sensorimotor Polyneuropathy The easiest way to classify diabetic neuropathy is with three different categories. Distal symmetric sensorimotor polyneuropathy is by far the most common form. It involves sensory loss in a distal symmetric fashion. This neuropathy occurs early in the disease and tends to progress as the disease exists for a longer and longer period of time. Motor weakness is an unusual characteristic, less prominent than the sensory component, and when it occurs it is distal as well. It occurs in a symmetric fashion but usually appears very late in contrast to the sensory abnormalities, which occur early and are usually quite mild. Pain symptoms are generally either absent or mild, although in a subcategory of cases they can become very severe and troubling. Although painful neuropathy may be the most evident form of diabetic neuropathy in those patients in whom it occurs, it actually represents a minority of the cases of diabetic neuropathy. The majority of the other types are much less evident from a symptomatic point of view.

An example of an unusual manifestation of distal symmetric sensorimotor polyneuropathy is a thermal burn from a cigarette in a patient who had sensory impairment and decreased thermal sensation. The patient never realized that he was burning himself until he smelled burning skin; he had no symptoms of pain. The neuropathy can be totally devoid of symptoms until some secondary injury supervenes as a result of the neurologic impairment.

As an example of distal motor weakness, a patient may show peripheral muscle atrophy in the feet, or loss of the intrinsic muscles in the foot, and may present with instability of gait, a feeling of instability, and falling. The diagnosis is clear just from examination of the feet.

Distal symmetric sensorimotor polyneuropathy can be divided into subgroups depending on which nerve fibers are affected. There are large myelinated fibers in the peripheral nerve, as well as small myelinated and unmyelinated fibers, and they serve different functions. Involvement of those fiber subpopulations will produce different clinical manifestations. Patients who have primarily small fiber neuropathy involving A-delta and C fibers will demonstrate impaired pain and temperature sensation, like the patient with the thermal burn. This neuropathy will often be accompanied by autonomic symptoms. Patients in another subclass of diabetic distal symmetric sensorimotor polyneuropathy primarily have large fiber involvement, and they may have impaired vibration and proprioception sensation. Those patients may present with gait disturbances, have absent Achilles tendon reflexes, and be asymptomatic. Most cases of diabetic distal symmetric sensorimotor polyneuropathy are mixed, showing both large and small fiber involvement.

An unusual characteristic of diabetic sensorimotor polyneuropathy should lead the clinician to think that perhaps another disease is present. Diabetic distal symmetric motor polyneuropathy is unlikely if there is more upper- than lower-extremity involvement, if there is more motor than sensory involvement, if the involvement is asymmetric, or if it is rapidly progressive. In such cases, the physician should consider additional diagnostic testing and neurologic consultation. A patient who presents with primarily unilateral wasting of the muscles in the upper extremity is unlikely to have diabetic distal symmetric polyneuropathy, but rather focal compression neuropathy, and this patient deserves more diagnostic attention than the usual patient with distal symmetric polyneuropathy.

Focal Neuropathy Focal diabetic neuropathy can be divided into four categories: (1) cranial neuropathy, (2) radiculopathy, (3) plexopathy, and (4) mononeuropathies.

Cranial Neuropathy. Cranial neuropathy is most commonly seen in elderly patients with type 2 diabetes mellitus. The ocular motor nerve is most commonly involved, usually but not always unilaterally. Cranial neuropathy is usually self-limited, with sudden onset and gradual resolution. It is clearly distinct from the slowly progressive distal symmetric polyneuropathy described earlier. A patient with diabetic ocular motor palsy may present with unilateral ptosis or diplopia and, at times, very severe headache. Diabetic ocular motor palsy has a sudden unilateral onset with headache, ptosis, and diplopia. The differential diagnosis is an internal carotid aneurism, which usually resolves spontaneously over a period of several months. Other cranial nerves can be involved with similar types of presentations, and they usually resolve spontaneously.

Radiculopathy. Diabetic radiculopathy also is usually seen in elderly patients with type 2 diabetes mellitus. It is almost always superimposed on mild, moderate, or severe distal symmetric sensorimotor polyneuropathy. It usually has a sudden onset with a slow or incomplete resolution.

Thoracolumbar radiculopathy is another form of focal radiculopathy that can occur in patients with diabetes. It usually causes unilateral pain with or without sensory loss in a dermatomal distribution. It may or may not be accompanied by motor impairment, and the differential diagnosis usually is a thoracic or abdominal disorder. For example, patients with severe left-side chest pain may be evaluated for myocardial infarction when in fact they have thoracic radiculopathy.

Patients who have abdominal radiculopathies may be evaluated for intra-abdominal emergencies such as cholecystitis when in fact they have a neurologic disorder. The key finding is decreased sensation over the distribution where patients have the pain, which can be detected by careful examination with a pinprick.

Lumbosacral Plexopathy. Diabetic lumbosacral plexopathy is also called diabetic amyotrophy, especially if it involves both lower extremities. Patients with this condition usually present with severe unilateral or bilateral muscle wasting and proximal muscle weakness. They may have tenderness over the femoral nerve, and in a couple of cases that have come to autopsy it was possible to demonstrate a series of vascular occlusions involving both the femoral nerve and the lumbosacral plexus. This condition may occur in the setting of severe weight loss and may be accompanied by severe depression, especially in older patients. In most cases, it resolves spontaneously over a period of six to 18 months, usually with relatively minor residuals.

Mononeuropathies. Mononeuropathies such as median nerve palsy ("carpal tunnel") occur with greater frequency in patients with diabetes. Vascular autonomic involvement can produce arresting tachycardia, which can be disabling, especially to young patients, and orthostatic hypotension. There is an increased frequency of sudden death. There may be gastrointestinal involvement, with severe gastroparesis at times or constipation and diarrhea. Constipation is probably the most common autonomic symptom in patients with diabetes. Bladder dysfunction is also very common in patients with diabetes. Impotence probably affects at least one-third of all men who have diabetes. Other peripheral autonomic manifestations can be the presence of edema or dry skin, as described earlier.

Not surprisingly, autonomic neuropathy with symptoms produces a marked increase in mortality. In a study of a small number of patients over 10 to 15 years of follow-up, those who had symptomatic autonomic neuropathy had a mortality rate of about 26%—much higher than patients who did not have autonomic neuropathy.

Foot Problems Probably the most serious problem that stems from diabetic neuropathy involves the feet, and in fact, as mentioned, foot problems are the most common cause of hospitalization for diabetic patients. Diabetic neuropathy likely accounts for more than 50,000 amputations in the United States every year; 50% of all nontraumatic amputations occur in diabetic patients and are the result of diabetic neuropathy.

Insensitivity The insensitive foot is a major concern in terms of amputation and ulceration. Inability to perceive the 10-g or number 5.07 monofilament at dorsal and plantar sites is the most accurate way of diagnosing foot insensitivity in patients with diabetes. This test should be part of the examination of every diabetic patient. Inability to perceive a 128-hz tuning fork is another good indicator that there is insensitivity and defines the high-risk foot. Patients with insensitivity are the ones that physicians need to focus on, the ones who need to be given detailed and repeated instructions during the foot examination. The test will also predict foot ulceration and amputation due to diabetes. Those outcomes are almost entirely preventable with appropriate prophylactic care.

Deformities In addition, doctors need to be able to recognize the characteristic foot deformities associated with diabetic neuropathy that place patients at risk for amputation and ulceration. These deformities include prominent metatarsal heads, cocked-up toe, or claw-toe deformities, bunions, and calluses. To make the diagnosis of diabetic neuropathy, the physician needs only to have the patient take off his or her shoes and socks to see what is hiding inside the shoe. Inspection can pick up most foot deformities, including callus.

Callus A diabetic plantar callus is defined as hyperkeratotic skin under a bony prominence or a weight-bearing area. Sometimes the physician does not need to look at the foot but can look at the shoe instead. An ulcer may form where the callus is; this is the telltale footprint of diabetes. The callus may break down because of the presence of autonomic neuropathy, dry skin, fissuring, opening, entrance of infection, and osteomyelitis.

All of these conditions are preventable through the use of orthotic devices to shift weight bearing off the head of the metatarsal; careful professional pruning of the callus; and lubrication of the feet to prevent breakdown and fissuring of the callus. Those measures will prevent ulceration, infection, osteomyelitis, and amputation.

Foot screening, however, is required because of the absence of neuropathic symptoms. Many patients who have diabetic foot ulcerations do not complain of pain or numbness or tingling. They simply have sensory impairment, structural abnormalities of the feet, or dry skin due to diabetic autonomic neuropathy. They will not report these conditions; the feet must always be examined.

The high-risk foot, then, is defined as having a callus or deformity plus insensitivity. Such conditions should trigger a mandatory podiatric referral, specifying the reason for the referral. The physician should request callus removal from insensitive feet and the use of inserts to redistribute weight off the heads of the metatarsals where callus is forming. These steps can prevent diabetic foot ulceration.

Differential Diagnosis Clinicians need to rule out other metabolic neuropathies, uremia, vitamin deficiencies, hypothyroidism, and other rare diseases such as acute intermittent porphyria. Toxic neuropathies also need to be ruled out (heavy metal neuropathies, other industrial hydrocarbon exposures). In addition, alcohol is one of the most important things to rule out in patients who present with diabetes and peripheral neuropathy. Infectious agents and inflammatory neuropathies need to be considered as well.

For example, physicians should order a simple test such as sedimentation rate to look for underlying vasculitis, lupus, or other diseases. The physician also needs to think about the variety of cancer-related neuropathies and anemias. In older patients with anemia, a serum protein electrophoresis is indicated, and one needs to look at blood smear amyloidosis, too. Hereditary neuropathies need to be ruled out based on the usual diagnostic approaches and history.

As for those who present with unusual neuropathies, a patient may have a severe weakness and diabetes. Motor neuropathies need to be considered. Most patients who have autonomic neuropathy will also have distal symmetric polyneuropathy, which can be detected. If a patient presents with autonomic neuropathy and no somatic neuropathy can be easily seen, it is most likely that the patient has a mild small-fiber distal symmetric polyneuropathy that is difficult to diagnose. So if a physician sees a patient with intact perception and intact sensation to a tuning fork test and yet he or she has autonomic neuropathy, the physician should check temperature sensation because he or she may have a small-fiber neuropathy. Another diagnosis to consider is idiopathic orthostatic hypotension. Patients may have abnormal electrodiagnostic tests. For most patients, it is not necessary to perform those tests clinically unless there is an unusual manifestation of neuropathy, but they are used frequently in clinical trials, as are measures of quantitative sensory testing. No quantitative sensory testing device has been developed that can be used in the everyday clinic, although research is moving in that direction. Autonomic function tests are sometimes valuable in looking at patients in clinical trials or in response to therapy. They can be useful in evaluating patients preanesthesia. Some patients may have a subclinical neuropathy.

What is really needed is an easy way to screen patients for diabetic neuropathy in the clinic. Recently, some instruments have been developed. One of these instruments was published recently by Young et al. Another one published several years ago from the author's own institution is the Michigan Neuropathy Screening Instrument, described in Diabetes Care. It consists of a patient self-administered questionnaire with 15 items, along with a simple physical examination of the foot that can be performed by a physician or a nurse. In the foot inspection, one should look for deformity, dry skin, callus, infection, fissure, and the presence or absence of foot ulceration, the presence or absence of reflexes, and the presence of abnormal or normal vibration perception or pressure perception at the great toe. A patient who has more than seven out of 15 positive answers or a person who has more than two points on the foot examination has a high likelihood of having diabetic neuropathy. This screening is being used in the follow-up on the DCCT, in the long-term follow-ups on a variety of other studies, and in some clinics on a weekly basis.

Summary Diabetic neuropathy is an important medical and public health problem. It complicates both type 1 and type 2 diabetes. It includes a variety of well-defined clinical syndromes that must be recognized. Distal symmetric sensory motor polyneuropathy is the most common. Most cases are asymptomatic and need to be detected on examination. It is a diagnosis of exclusion. Classification is based on the distribution of neurologic deficits. Currently, screening tools are available to detect at-risk populations.

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Dr. Greene is Professor of Internal Medicine at the University of Michigan, Ann Arbor. Address for correspondence: D.A. Greene, MD, 3920 Taubman Center, Box 0354, University of Michigan, Ann Arbor, MI 48109-0354.

Annals of Long-Term Care - ISSN: 1524-7929 - Volume 8 - Issue 05 - May 2000