Getting a Grip on Peripheral Neuropathy

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By Miki Fairley

Peripheral neuropathy (PN) presents in astonishing variety—more than 100 types have been identified, each with its own characteristic set of symptoms, pattern of development, and prognosis, according to the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH).

Peripheral neuropathy describes damage to the vast, complex communication system that transmits messages both to and from the brain and spinal cord comprising the central nervous system (CNS).

To give a better picture, here is an overview:

Peripheral neuropathies can affect the sensory or motor-neuron cell bodies (neuronopathy), their axons (axonal neuropathies), or their myelin (demyelinating neuropathies).

Two broad classifications are mononeuropathies, in which one nerve trunk is involved, and the much more common polyneuropathies, in which multiple nerves are involved.

In the most common forms of polyneuropathy, the nerve fibers farthest from the CNS malfunction first, according to NINDS. Pain and other symptoms often appear symmetrically in both feet, followed by a gradual progression up both legs. Next, fingers, hands, and arms may be affected, and symptoms may progress into the central part of the body. "Many people with diabetic neuropathy experience this pattern of ascending nerve damage," NINDS notes.

Impaired function and symptoms depend on the type of nerves involved—motor, sensory, or autonomic. Although some neuropathies may affect all three types of nerves, others primarily affect one or two types.

PN can be genetic or acquired. Acquired PN is grouped into three broad categories: those caused by systemic disease; those caused by trauma from external agents; and those caused by infections or autoimmune disorders affecting nerve tissue. A large fourth category is idiopathic although research is revealing some of these etiologies.

Acquired PN can result from a wide range of causes, including tumors, toxins, trauma, autoimmune responses, nutritional deficiencies, alcoholism, viral and bacterial infections, and vascular and metabolic disorders. The prognosis of neuropathy can differ depending on the etiology. In some cases, neuropathy is reversible, and often the progression can be slowed or even stopped by proper etiology-based treatment, according to the article, "Essential Insights on Detecting the Etiology of Peripheral Neuropathy," by Jeremy Tilton and Lee C. Rogers, DPM, in Podiatry Today, March 2009. Accordingly, it is crucial to determine the specific cause or causes of each patient's neuropathy. However, as the article points out, this task is complicated by the fact that neuropathy can be a master of disguise: the same neuropathy can be caused by different diseases, and the same disease can cause several different neuropathies.

Peripheral neuropathy due to diabetes type 2 (diabetes mellitus) is the form most commonly encountered by O&P practitioners and pedorthists, since it often causes foot deformities and leads to foot ulcerations which, without proper care and treatment, can lead to amputations.

About 60-70 percent of persons with diabetes have nervous system damage, ranging from mild to severe. Almost 30 percent of persons over age 40 with diabetes have impaired foot sensation, and, as is well known in the O&P and pedorthic professions, diabetic neuropathy is a leading cause of lower-limb amputations. In fact, according to the Amputee Coalition of America (ACA), the lion's share—over half—of all amputations in the United States are caused by diabetes mellitus and subsequent complications.

What Is Happening to the Nerves?

To solve any problem, it is first necessary to understand it. So, what exactly happens to a peripheral nerve when neuropathy occurs? Each neuron has numerous dendrites that connect with other neurons, carrying nerve impulses to the cell body. A single long axon carries nerve impulses away from the cell body. Through electrochemical processes, nerve impulses are relayed across a gap, or synapse, from the axon of one neuron to a target cell, which can be another neuron, a muscle cell, or a gland cell.

Companion cells, the Schwann cells, wrap their membranes around the sensory and motor neuron axons, thus providing a thick, insulating lipid-protein layer, the myelin sheath. This protective layer prevents short-circuiting among axons and facilitates signal conduction. Breaks in the myelin sheath—the nodes of Ranvier—boost signals and allow them to travel to the next node. "They are like power-station relays," says James Hickman, PhD, a chemistry professor and bioengineer at the NanoScience Technology Center at the University of Central Florida, Orlando.

Diabetes-caused peripheral neuropathy can involve damage to the axons themselves or demyelination of the myelin sheath, or both. But just how hyperglycemia and elevated cholesterol and fatty acid levels act on the neurons to cause axonal damage and demyelination is not yet well understood. Gaining knowledge about the processes and factors involved would be a giant step toward finding pharmacological and other treatments to slow, reverse, or prevent PN.

An essential first step is to have lab-cultured neurons that myelinate and form nodes of Ranvier, so that, under controlled conditions, researchers can investigate various possible causes and solutions of demyelination. Although this has been achieved with sensory neurons, until a landmark breakthrough by Hickman and his research team, including graduate student John Rumsey, this had not been done with motor neurons.

This discovery opens the door to research to help identify what causes myelin to degrade; for instance, what happens when the cultured motor-neuron systems are treated with factors such as high concentrations of fatty acids and cholesterol found in diabetes. In turn, these results could help identify new drug therapies that could also be tested using the model. The model can help advance understanding of muscular dystrophy and other diseases as well.

Says Hickman, "We are trying to create systems that others can use for their research." If we can get better tools out there, the research will go faster to find ways to cure these diseases."

The Damage It Causes

Neuropathies, including those caused by diabetes, can have an alarming number of damaging—even life-threatening—consequences.

Motor neuropathy can cause progressive muscle atrophy and weakness, gait impairment, increased risk of falling, and foot deformities leading to ulceration, notes Podiatry Today.

Other symptoms may include painful cramps and fasciculations (uncontrolled muscle twitching visible under the skin), muscle loss, bone degeneration, and changes in the skin, hair, and nails, according to NINDS. These more general degenerative changes can result from sensory or autonomic nerve fiber loss as well.

Sensory neuropathy can result in feelings of numbness and loss of proprioception, thus impairing coordination of complex movements. Other effects can include neuropathic pain, which can be hard to control, cause sleep disruptions, and affect emotional well-being. Sensory neuropathy can lessen the ability to feel pain or changes in temperature, thus sufferers may not be aware of injuries or infected wounds. They may not even be able to detect pains that warn of an impending heart attack.

Autonomic nerve damage has diverse symptoms and can become life-threatening if breathing becomes impaired or the heart starts beating irregularly. Other symptoms can include incontinence, lack of ability to regulate blood pressure, and gastrointestinal problems.

A fourth type, focal neuropathy, results in the sudden weakness of one nerve or a group of nerves, causing muscle weakness or pain.

Prevention and Treatment

Photograph courtesy of Wayne Rosen, CPO, CPed, PA.

How close are we to solutions? Even though research has made advances in understanding and treatment potential, "optimal glycemic control remains the only available measure with proven efficacy in preventing or halting progression of diabetic neuropathy," points out the article "Advanced Diabetic Neuropathy: A Point of No Return?" by Petr Boucek in The Review of Diabetic Studies, Fall 2006. "However, to be effective, it should be instituted at an early stage, since, as is the case with other late complications of diabetes, the late phases of diabetic neuropathy are poorly reversible or even irreversible." And when nerves do regenerate, they may regenerate defectively, the article notes.

The landmark Diabetes Control and Complications Trial (DCCT), conducted from 1983 to 1993 and funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the NIH, reinforces Boucek's conclusion. The study shows that keeping blood glucose levels as close to normal as possible slows the onset and progression of the eye, kidney, and nerve damage caused by diabetes. Regarding diabetic neuropathy, the study results show the risk of nerve damage was reduced by 60 percent in people on intensive treatment to control blood glucose levels.

Orthotic, Pedorthic Perspective

Diabetes is a subject that really hits home for Wayne Rosen, CPO, CPed, PA, owner of a facility bearing his name in Pembroke Pines, Florida. He has seen first-hand the grim effects of the disease on beloved family members as well as patients. For this reason, he is passionate about educating patients about the disease, its care and treatment, and the havoc it can wreak on patients who are noncompliant.

"Even more important than the prescription is patient education to bring about a good prognosis," Rosen says. "It doesn't take long to go from nothing to a grade 1, and from grade 1 to a grade 3," he adds, referring to the Wagner Ulcer Grade Classification System for classifying depth and infection in dysvascular and diabetic foot ulcers. Grade 1 wounds are defined as superficial ulcers with no subcutaneous tissue exposure; grade 2 wounds involve penetration through the subcutaneous tissue and may expose bone, tendon, ligament, or joint; grade 3 wounds involve osteitis, abscess, or osteomyelitis; grade 4 wounds involve gangrene of the forefoot; and grade 5 wounds involve gangrene of the entire foot, according to the Society for Vascular Surgery. Patients need to be educated to the vital necessity of keeping blood glucose levels at or near normal, being compliant with treatment protocols, and being alert to any emerging or worsening symptoms of diabetic complications.

Diabetes is insidious, often lulling patients into a false sense of security, since the impact on overall well-being and function is little or none—at first. This, coupled with the human tendency to go into denial when confronted with a serious disease, often causes patients to minimize the disease in their mind and thus not take treatment compliance seriously. This is especially true, Rosen says, if they are first diagnosed at a relatively young age, such as in their still-vigorous and otherwise healthy 40s, for instance. As he puts it, "They say, 'Hey, I feel fine! No worries!" But over a period of time, perhaps years, diabetes does its damage, and by the time patients are aware of what's happening, they may already be in serious trouble.

The same mindset can affect patients with loss of sensation in their feet. "Why check my feet if they don't hurt?" Many orthotists and pedorthists can tell stories of patients going around with nails in their feet or other injuries, blissfully unaware. Rosen remembers a patient mentioning the bad day she was having, including losing her car keys. When Rosen checked her feet—there in her shoe were the missing keys!

Prescription Considerations

Physicians often recognize the value of input from orthotists and pedorthists when it comes to prescribing diabetic foot treatment. The team setting in a clinic is best, Rosen says, since everyone is present to discuss and develop an optimal treatment plan. But even when a team setting is not available, physicians often rely on the orthotist's or pedorthist's expertise. Rosen estimates physicians request his input about 90 percent of the time.

"Our ability to make recommendations in the orthotic prescription is the best possible option to ensure successful outcomes," says Roger Marzano, CPO, CPed, Yanke Bionics Inc., Akron, Ohio. "We often get prescriptions that have incomplete diagnoses or unclear orthotic direction, and look at that as the opportunity to discuss the prescription with prescribing physician."

Physicians often write a general prescription and leave the details to the physical therapist, orthotist, or pedorthist, notes David Sinacore, PhD, PT, FAPTA, director of the Applied Kinesiology Laboratory, University of Washington, St. Louis, Missouri.

What to take into consideration first in prescribing orthotic care for diabetic foot conditions is "sort of like real estate," Sinacore says. "It's location, location, location." Where the problem occurs and whether or not an ulcer is present are the primary considerations.

Besides the patient's ambulatory and ischemic status, Marzano says other concerns include whether or not an ulcer is present; the presence of any structural deformities, such as equinus, valgus, or varus; motor status, such as drop foot and ankle instability; and any neuropathic upper-limb involvement. Social factors, such as living alone, ability to drive, and work requirements are also important.

Roger Marzano, CPO, CPed, fits a thermoplastic AFO on a patient with peripheral neuropathy and drop foot. Photograph courtesy of Yanke Bionics, Akron, Ohio.

In addition to specific diabetic foot aspects, Rosen also stresses the importance of considering the patient's weight, ability to don and doff orthoses or remove shoes, availability of transportation to appointments, and need for assistive devices if the patient has trouble seeing his or her feet, removing shoes and socks, poor eyesight, and other difficulties.

Although a detailed analysis of orthotic designs and applications is outside the scope of this article, The O&P EDGE asked several pedorthic experts for a list of some things to be careful about or avoid.

Rosen advises avoiding plastics, since the lack of flexibility can cause pressure sores, blisters, and other skin issues leading to further complications if orthoses are poorly designed or fitted. "I'm not saying we don't use plastics, because we do. There's a place for plastics, but using plastics when there is loss of sensation due to neuropathy is dangerous unless you have a well-educated patient and a well-trained practitioner."

To Sinacore, putting carbon plates inside the shoe is a definite no. It is better and safer to split the outer part of the sole and embed the plate in the sole for needed stiffness while still protecting the diabetic foot, he points out, even though this is more time-consuming.

"Certainly, I would hesitate to make a definitive AFO or footwear if patients have an ulcer due to dressing bulk, edema relative to cellulitis, infection, or uncontrolled lymphedema," Marzano says. "I would recommend temporary devices or footwear until their condition stabilizes or is more appropriate for off-loading a wound, or until the edema is properly managed."

Summing up the goal of orthotic/pedorthic care, Rosen says, "We have a responsibility to the patient—to give him or her every opportunity to succeed."

Miki Fairley is a contributing editor for The O&P EDGE and a freelance writer based in southwest Colorado. She can be contacted via e-mail at