Keeping on Top of Neuropathy

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Most people with diabetes aren’t fully aware of the dangers of diabetic nerve damage, or neuropathy, which include impotence, heart-rhythm abnormalities, and amputations. Neuropathy affects 90% of people who have had either Type 1 or Type 2 diabetes for more than 10 years, although the symptoms can be subtle or even absent. Most commonly thought of as a foot-care issue, neuropathy actually has several forms and can affect many parts of the body. New tests make diagnosing neuropathy easier, yet long-available, simple tests are still effective and underused weapons.

Even though current knowledge of treating neuropathy lags behind knowledge of how to diagnose it, knowing you have neuropathy is valuable because it allows you to take steps to prevent more serious complications. This article describes two general forms of neuropathy, peripheral and autonomic, and some of the tests used to diagnose them.


Peripheral neuropathy

Peripheral neuropathy, which affects the feet, legs, and, less commonly, the hands, is dangerous because its symptoms can be so subtle. In fact, the “symptomless” foot is most likely to have a problem.

“Pain is what takes most people to the doctor’s office,” says John B. Perry, DPM, a podiatrist in Portland, Maine, who specializes in diabetic foot care. “If it doesn’t hurt, you don’t come in. The problem is, people with diabetes don’t have the same sensations in their feet. You have to check and have them checked when they don’t hurt.

“I tell people with neuropathy that the nerves in their feet aren’t sending information anymore,” he says, “and that they have to use their brain and their eyes and their fingers to save their feet.”

The damage and the danger from diabetic peripheral neuropathy comes from two basic problems: loss of nerve function and loss of blood supply. Both are caused by the primary dysfunction of diabetes: too much glucose in the blood.

The damage that high blood glucose levels do to the nerves is a complex and still not fully understood cascade of cellular events that is often described as a “dying back” of the nerve fibers. The nerve fibers, the insulating layer that surrounds them, and the cell bodies that supply the nerve with food and fuel, die off. The damage begins at the ends of the longest nerves — those that go to the toes — first, but can eventually affect any and all parts of the peripheral nervous system.

Diabetes also reduces blood flow to the nerves and to the extremities. This contributes to neuropathy and injury, and also affects the body’s ability to heal injuries.

Foot disease caused by neuropathy is the most common complication leading to hospitalization of people with diabetes, but according to the National Institutes of Health, only half of people with diabetes check their feet daily. Each year, some 86,000 Americans with diabetes have a lower-extremity amputation, and up to 85% of those losses could have been prevented.

The first and most important step to protecting the feet is preventing injury, whether or not neuropathy has been diagnosed. The most common cause of injury to the feet is improperly fitting footwear. People who do not have neuropathy respond to repetitive stress or pain in their feet by shifting their weight or posture, adjusting their gait, or fixing their shoes. A person with neuropathy does not have the same sensations of pain or discomfort, so the stress goes unrelieved and progresses to a blister or sore, which can develop into an ulcer that requires medical attention. People with diabetes are particularly prone to foot problems as they age, so vigilance becomes ever more important.

“Even without diabetes,” Dr. Perry says, “the feet have wear and tear from aging. The toes contract and become less flexible, and where a flexible toe moves with shoe gear, a rigid toe rubs against it. Our arches flatten as we age, and the foot widens. Without diabetes, someone can feel the effects of these changes. With diabetes, they don’t feel them, and they’re at risk for a blister or a callus.

“Visual deficits from aging might prevent someone from seeing a blister or a cut on his foot,” he says. “Loss of flexibility might make it harder to look at the bottom of the feet. Even a diminished sense of smell, a normal part of aging, can prevent someone from smelling an infection.”

Diagnosing peripheral neuropathy

The American Diabetes Association recommends that all people with diabetes have a foot examination every year. Those with diagnosed neuropathy should have a foot examination at every visit with a health professional. That examination should include at least a crude test for loss of sensation, and some professionals believe that more sophisticated tests should be included as well.

There are several relatively simple ways to assess the loss of protective sensation that signals peripheral neuropathy. Among the simplest and easiest to administer is the Semmes-Weinstein 5.07 (10-gram) monofilament test. The monofilament is a piece of nylon that is designed to bend as its tip is pressed against the foot.

The test is simple: the person lies down or sits barefoot, with legs extended and supported. The examiner presses the monofilament against four to ten locations on each foot and records whether the person feels the pressure. The filament bends at 10 grams of force, which can be felt by most people with intact nerve function. A secondary but equally important benefit to the monofilament test is that it causes the examiner to take a close look at the feet.

Vibration testing with a tuning fork is another simple test for loss of sensation. The fork is struck and applied to various parts of the foot or leg. The person having the test reports his perception of both the start of vibration and the cessation of vibration.

A professional can also test pain perception by pricking a person’s skin with a sterile needle.

An annual examination should also include checking pulses in each foot to check the blood supply to the feet. If a problem is found, more complicated studies can be done to pinpoint the cause.

Joseph C. Arezzo, PhD, Professor of Neurology and Neuroscience at the Albert Einstein College of Medicine in New York City, cautions that while the monofilament and other simple tests for sensation have value, they fall short of a complete assessment.

“For a rapid and simple screening, it’s a useful technique,” he says, “but it can only tell you gross abnormality. That’s important because if you’re diabetic and have neuropathy, it’s almost immediately assumed that it’s due to diabetes. In fact, you could have an asymmetric neuropathy, or a slipped disk, or a nerve root disease. In other words, people with diabetes can have anything else that can go wrong with anyone. If you assume the loss of sensation is due to diabetes, you could miss the other problems.”

Diabetic peripheral neuropathy is symmetrical, so Dr. Arezzo says that a screening should determine if the loss of sensation is worse on one side than the other, which might indicate a different condition. Likewise, diabetic peripheral neuropathy is usually worse the further you go toward the foot, so if it is not, that could also indicate the need to look for another problem.

“You need to look at the progression and severity, which can be done as simply as adding different monofilaments that bend at lower forces,” he says, “and you should test not just both feet, but both ankles and both knees.”

The “gold standard” for assessing neuropathy is to assess a person’s electrophysiology by directly measuring nerve conduction and the strength of nerve signals. A nerve conduction study tests the response of muscles to mild electrical shocks, which are delivered through pads placed on the skin. The person indicates when he feels a tingling sensation, which may or may not be painful. A more invasive examination involves inserting thin needles into the muscle to measure the nerve conduction and does not involve electricity. The only pain associated with this test is that of the actual insertion of the needle through the skin.

“Electrophysiology is getting simpler and more likely to be available in the primary practitioner’s office,” Dr. Arezzo says. “There is a handheld device that is available now. Sensory evaluations are also going to become more practical, more computerized, and simpler to do.”

Another approach is quantitative sensory testing, which measures and evaluates responses to stimuli such as hot and cold, vibration, and pain. Computerized analysis and standardized threshold levels have made these tests much more useful, and people with diabetes are more and more likely to see them in their physicians’ offices.

There are shortcomings to sensory testing, and so researchers continue to look for more sensitive and definitive measures of nerve function. For instance, electrophysiological exams assess myelinated fibers (nerves within a sheath), but it may be that neuropathy is evident first in small, unmyelinated nerve fibers, such as certain nerves that feed the blood vessels in the skin.

“These smaller fibers escape the attention of a standard electrophysiological test,” says Aaron I. Vinik, MD, PhD, Director of the Diabetes Research Institute of the Strelitz Diabetes Institutes at Eastern Virginia Medical School in Norfolk, Virginia. “Diminished blood flow in the skin, which is regulated by these small, unmyelinated nerve fibers, is one of the earliest abnormalities you can detect in diabetes.”

There are several means of measuring the status of these nerves, including laser Doppler measurement of blood flow. “It’s going to take a long while before this becomes standardized and can be used in clinical practice,” Dr. Vinik says, “but it’s easy to perform, it’s not invasive, and it can be done in a doctor’s office in 10 or 15 minutes.”

Other, more esoteric, measurement methods used by researchers to evaluate nerves include microdialysis and iontophoresis, but Dr. Vinik believes they will remain research tools only. However, he predicts that another technique called a skin punch biopsy will eventually become commonly used. According to Dr. Vinik, “The appearance of the small nerve fibers in the skin can tell you more about them than anything else, and skin punch biopsy is being used in research settings to actually see them. It could eventually be done in the office in less than five minutes with a little local anesthesia, and you could actually count the number of nerve fibers.”

Active participation is foremost

Diabetes care is a team effort, and in the prevention of foot disease, the individual with diabetes who is educated and aware is the most effective member of the team.

“The more you know, the better,” Dr. Perry says. “Here in Maine, we’ve documented a 51% increase in the utilization of podiatrists after a patient goes to Ambulatory Diabetes Education classes. Some studies have found a 63% improvement in amputation avoidance when the patient sees a professional for foot care, so the potential benefit of education to patients is tremendous.

“There is a tremendous amount of denial about foot problems, especially in men over 50. They’re afraid of what it means, that if they report a problem they’re going to lose their foot. Some of that is, frankly, justified, because the surgical approach — amputation — is still the first resort of many medical professionals. But amputation is not inevitable. Our first goal is to save the foot.”

The science of wound care has improved greatly in the past few years, along with the science of prevention. Ulcers that once were certain to lead to amputation can now be healed, and there are many simple, noninvasive ways to prevent ulcers in the first place.

“We have a lot of tools at our disposal,” Dr. Perry says. “The right shoes, inserts, physical therapy, and stretching, for instance. We might be able to recommend prophylactic surgery to straighten a contracted toe that would otherwise be at risk, or lower limb bypass surgery to improve blood flow. We know a lot more about wound care today, and there are new medications that actually help regrow skin to cover wounds.”

Autonomic neuropathy

Less well known, and perhaps more dangerous even than peripheral neuropathy, is autonomic neuropathy. This condition affects the autonomic nerves, the nerves that regulate involuntary body functions and systems such as the digestive system, the sexual organs, the urinary tract, the heart, and the sweat glands. Symptoms come in a wide variety of forms, including sexual dysfunction, delayed emptying of the stomach, diarrhea, and difficulty urinating.

Cardiac autonomic neuropathy, an important factor for cardiovascular mortality in people with diabetes, may cause “silent” heart attacks because people with this form of neuropathy don’t feel cardiac pain. Moreover, neuropathy may affect the ability of the heart to vary its rate in response to exercise or a change in position. This loss of heart-rate variability is predictive of serious cardiac problems.

“I believe that measurement of heart-rate variability will become a standard of care in due course,” says Dr. Vinik. “It was very difficult to do in the early days, but now there are several machines available that can do it in the doctor’s office in 10 or 15 minutes. You get a standardized report that gives you a number, and I believe that this number will be known as commonly as those for cholesterol, blood glucose, or hemoglobin A1c.

“In our practice,” he says, “every person with autonomic neuropathy gets a heart-rate variability test, as does every person who has had diabetes more than five years. Every person with Type 2 diabetes gets the test on the first day we see them because they may have had diabetes for seven or eight years already. There are a number of treatment options for improving heart-rate variability.”

Another form of autonomic neuropathy and a debilitating late-onset complication of diabetes is gastroparesis, a paralysis or dysfunction of the stomach that causes food to move through the digestive tract either too slowly or not at all. Serious cases are readily diagnosed, but more commonly, gastroparesis (or gastropathy) is subtle, causes unpleasant symptoms, and interferes with blood sugar control because food absorption is delayed.

At one time, the only way to diagnosis gastroparesis was with a complicated procedure that examined the different phases of contraction of the stomach and could only be done in a research laboratory. Then researchers developed the electrogastrogram, which is similar to an electrocardiogram. They found that the stomach could be subject to rhythm disturbances much like those of the heart: tachygastria (fast contractions), bradygastria (slow contractions), or gastric arrhythmia (irregular contractions).

“Unfortunately, there is no specific therapy for stomach arrythmias as yet,” Dr. Vinik says, “but we’re hopeful that they will be developed.”

Measurement and diagnosis of both peripheral neuropathy and autonomic neuropathy continues to advance. Right now, as always, the vigilance of the individual who has diabetes and the rest of the health-care team is the best prevention. Click here for a list of foot-care tips that can help you get started.

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