Dr. Steven J. Dolgoff
Peripheral-Neuropathy
the challenge

Defining the Challenge

Definition and Prevalence

DPN is often defined as “the presence of symptoms or signs of peripheral nerve dysfunction in patients with diabetes after the exclusion of other causes.” There are several challenges to using this definition. Clinicians detect peripheral nerve dysfunction based on patients’ presenting symptoms and/or physical examination. Most often, symptom- and/or physical examination–based scales are used, but these may lack sensitivity. Some experts advocate using a large panel of different tests together to maximize sensitivity, and scales may be supplemented by electro diagnostic studies such as nerve conductions, electromyography (which is sensitive for large-diameter sensory and motor fiber dysfunction), autonomic testing, and epidermal nerve fiber density testing (which is sensitive for small fiber dysfunction).

A second challenge comes from the “exclusion of other causes.” Diabetes mellitus can affect sensory nerves, motor nerves, and autonomic nerves. Distal symmetric polyneuropathy typically leads to both small and large nerve fiber damage. Frequently, combinations of nerves are affected in what is termed polyneuropathy.

Classification systems have been proposed based upon the types and patterns of peripheral nerves involved. For every one of these sites of pathology, there will be a list of potential causes. A detailed description of all the causes of every type of peripheral nerve dysfunction that can be seen in a patient with diabetes mellitus is beyond the scope of this monograph. However, there are certain patterns of neuropathy that are highly unlikely to be related to diabetes mellitus. The most common presentation of DPN (and its differential diagnoses) is presented later in this monograph.

The challenges of the definition of DPN, as the challenge of ascertainment bias, make the true prevalence of DPN difficult to know. Dyck and colleagues attempted to determine the extent of diabetic neuropathies in a community-based study of 380 patients with clinically recognized diabetes mellitus. Of these patients, 102 had insulin-dependent diabetes mellitus(IDDM), and 278 had non–insulin-dependent diabetes mellitus (NIDDM). Two-thirds of the IDDM patients had some type of neuropathy; of these patients, 54% had polyneuropathy, 22% had asymptomatic carpal tunnel syndrome, 11% had symptomatic carpal tunnel syndrome, 7% had visceral autonomic neuropathy, and 3% had other neuropathies. Patients with NIDDM had similar rates of neuropathies: polyneuropathy (45%), asymptomatic carpal tunnel syndrome (29%), symptomatic carpal tunnel syndrome (6%), visceral autonomic neuropathy (5%), and other neuropathies (3%).

DPN Presentation Is Typically Sensory and Insidious in Onset

Chronic sensorimotor polyneuropathy is the most common form of DPN. Up to 50% of the patients with this type of neuropathy experience painful symptoms such as burning pain, electrical or stabbing sensations, paresthesia, hyperesthesia, and deep aching pain. From 10% to 20% have symptoms severe enough to require treatment. In most patients, the pain is worse at nighttime.

DPN presentation is mainly sensory and insidious in onset. Symptoms begin in the toes and the feet and gradually extend proximally.10 Later, the fingers and hands may become affected, again with proximal spread. Usually, when extensive, the anterior abdominal wall may be involved, and sensory loss gradually spreads laterally around the trunk. Patients may lose their ability to feel, identify, or manipulate smaller objects. They can gradually lose the capacity to ascertain temperature or sense painful or threatening stimuli. The loss of innervation can lead to atrophy of essential pedal muscles, resulting in deformities (eg, hammertoes) that leave patients vulnerable to ulceration. Sensorimotor neuropathy is the main risk factor for developing diabetic foot ulcers, which are the predominant risk factor for lower-extremity amputations in diabetes patients.

Motor involvement is less frequent than sensory involvement. However, when severe, this neuropathy causes weakness of distal leg muscles.

Autonomic Neuropathies

The autonomic nervous system may become widely involved itself in diabetic neuropathy. Diabetic autonomic neuropathy can develop in patients with type 1 or type 2 diabetes. While autonomic neuropathy can occur at any stage of diabetes, those over age 40 years who have had the disease for more than 25 years and have difficulty control- ling their blood sugar run the highest risk.

Most patients have symptoms that are not severe, but some have significant morbidity and even mortality, especially with cardiovascular autonomic neuropathy (CAN). Symptoms of autonomic neuropathy range from cardiac (ie, early fatigue, weakness with exercise, and postural hypotension) to gastrointestinal (ie, gastroparesis, erratic glucose control, abdominal pain, early satiety, nausea, vomiting, constipation, and diarrhea). Other symptoms include sexual, bladder, and sudomotor dysfunction.

Cardiovascular Autonomic Neuropathy

CAN affects both the sympathetic and parasympathetic innervation of the heart and coronary vessels. Primary symptoms of CAN are orthostatic hypotension and decreased heart rate variability, and CAN may contribute to left ventricular dysfunction, silent or asymptomatic myocardial infarction, and exercise intolerance. There is evidence that the disease process may begin early in the course of diabetes but remains asymptomatic until later stages.

Gastrointestinal Autonomic Neuropathy

Diabetic autonomic neuropathy can affect the entire gastrointestinal system. Symptoms range from mild discomfort to disabling impairment of daily activities. Gastroesophageal dysfunction manifests as gastroesophageal reflux disease in roughly 30% of diabetes patients. Delayed gastric emptying and gastric retention, which are present in one-fourth of patients with diabetes, can result in early satiety, bloating, epigastric pain (heartburn), nausea, vomiting, and anorexia. Gastroparesis can also complicate pharmacotherapy by delay- ing the absorption of glucose or antidiabetic medication.

Focal Neuropathies

Diabetic mononeuropathy has an acute onset, usually is asymmetric, and involves the cranial, truncal, and peripheralnerves. The neuropathy generally resolves spontaneously in 3 to 12 months, but in rare cases may last for years.

Cranial Neuropathies

Cranial neuropathies are rare, and include the III, IV,VI, and VII cranial nerves. Cranial neuropathy affects the nerves connected with the brain that control sight, eye movement, hearing, and taste. Most often, cranial neuropathy affects the nerves that control the eye muscles. Neuropathy starts with pain on one side of the face near the affected eye. Later, the eye muscle becomes paralyzed, resulting in double vision. Nevertheless, symptoms of this type of neuropathy usually resolve within 2 or 3 months.

Truncal Neuropathies

Truncal neuropathy usually presents subacutely with painful paresthesia in variable size patches in the trunk, either unilaterally or bilaterally. Associated involvement of motor nerve fibers can lead to bulging of the abdominal wall in the paresthetic areas. Clinicians should check for a patch of sensory abnormality in the region of the symptoms.

Proximal Neuropathies

Proximal neuropathies may develop in long-standing diabetics with poor metabolic control and may lead to weight loss. A prominent feature is pain that is often severe and located in the hips and thighs. Proximal neuropathy causes weakness in the legs and often leaves patients unable to emerge from a sitting to a standing position without aid. The length of the recovery period varies, depending on the type of nerve damage.

Diagnosing Diabetic Neuropathy

Diagnosing diabetic neuropathy requires clinicians to perform a thorough physical examination, elicit patient history, and use clinical judgment; it does not necessarily hinge on any particular neurologic test or finding. Some patients present with severe pain but only minimal neurologic deficits, while others present with foot ulcers but have no pain or neurologic symptoms.

A complete medical evaluation enables clinicians to classify the diabetes, detect the presence of diabetes complications, review previous treatment and glycemic control in patients with established diabetes, assist in formulating a management plan, and provide a basis for continuing care.