An estimated 20 million people in the US have peripheral neuropathy. That is one in 15 persons. Patients presenting with symptoms referable to the peripheral nerves—which include numbness, pain, paresthesia, and weakness— are common in neurology practice. And yet, residency programs are skewed towards the diagnosis and management of inpatient neurological disorders, which means that practicing neurologists may not become comfortable with diagnosing and treating neuropathy until early in the course of practice.

This article provides an overview of neuropathy diagnosis and management. It will also offer strategies for talking to patients about the disease and avenues for addressing it therapeutically.

Making the Diagnosis

Neuropathy itself is not usually a disease but a symptom of an underlying illness. The most common cause is diabetes mellitus. Heavy alcohol use and inherited forms also top the list. Medication-associated neuropathy may be overlooked. When we speak of inherited neuropathies we must distinguish between neuropathy that is inherited as a disease unto itself, such as Hereditary Motor and Sensory Neuropathy, versus inherited illness that has neuropathy as a symptom, such as familial amyloidosis or Pompe’s disease.

In unpacking the word “neuropathy” we recognize that this word can mean a lesion of a single nerve (mononeuropathy), multiple nerves scattered throughout the body that are affected at different times (mononeuropathy multiplex), or a disease of all nerves (peripheral neuropathy, also called polyneuropathy or simply neuropathy). Within the diagnosis of peripheral neuropathy there are three types: axonal, demyelinating, and dysmyelinative (which describes inherited disorders of myelin). Demyelinating neuropathies account for approximately 10 percent of all acquired neuropathies. The most common type is axonal, length-dependent, dying back polyneuropathy, which account for almost 90 percent of acquired neuropathies.

Sensory symptoms that patients describe with axonal neuropathy can range from a feeling as if bugs are crawling on their skin to shooting, electrical, or burning pains. When autonomic nerves are involved, common symptoms include lightheadedness when standing or sitting up, dry eyes and mouth, diarrhea, difficulty with vision and, in men, erectile dysfunction.

On examination, characteristic findings include symmetrically depressed or absent tendon reflexes at the ankles, atrophy of the extensor digitorum brevis, weakness of distal muscles in the legs and decreased or absent sensation in a stocking distribution. In most axonal neuropathies, small fiber modalities such as pain and cold sensation are affected first with large fiber modalities of vibration and joint position affected later. Careful examination of cranial nerve III may reveal a partial palsy associated with diabetes. With autonomic involvement, the skin over the legs may be shiny and dry with loss of hair distally. In patients whose symptoms are caused by vitamin B12 deficiency, the exam may instead show decreased large fiber sensation with preserved small fiber sensation and brisk, rather than depressed, reflexes. This is due to subacute combined degeneration of the spinal cord. Patients with this topsy-turvy exam in the face of symptoms suggestive of neuropathy should have a careful diet history taken and vitamin B12 level checked.

Evaluation of peripheral neuropathy includes testing of blood and urine, nerve conduction studies, and electromyography and lumbar puncture, if demyelinating neuropathy is suspected. Routine blood testing includes complete blood count, thyroid stimulating hormone, renal functions and tests for diabetes including hemoglobin A1c, fasting glucose and two-hour glucose tolerance test. Then, obtain serology for human immunodeficiency virus and hepatitis C. Depending on the patient’s history, you may also investigate less common causes, such as heavy metal exposure and inherited neuropathy. While you can test for syphilis, it is important to note that syphilis does not cause neuropathy. Tabes dorsalis can cause “lightening pains,” shooting into the legs and trouble with balance, but these symptoms are different from symptoms of neuropathy and I do not typically obtain this test.

Nerve conduction studies and electromyography can characterize neuropathy as axonal or demyelinating, sensory or motor or both and can give an idea as to the severity and chronicity of the neuropathy. In addition, it can exclude neuropathy look-a-likes such as lumbosacral radiculopathy. Nerve biopsy is typically not necessary except in cases where infiltration of the nerve (such as with lymphoma or amyloid) or vasculitis is suspected and treatment depends on a tissue diagnosis.

Treatment Options and Patient Communication

In the treatment phase, management of patients’ concerns is essential. Over the years I have found that patients think about treatment of neuropathy from three perspectives. These are expressed in the following questions: “Can I treat the cause of neuropathy?” “What can I do to help the nerves grow back?” “What can I do about the pain, tingling, weakness and autonomic symptoms?” After the history, examination and testing reveal the type of neuropathy, we still may not know the etiology but we can address the patients’ questions.

If the etiology is known, it can be addressed: for example, with better glucose control, treatment of hepatitis C, Vitamin B12 repletion and cutting back or abstaining from alcohol. I like to use this time to empower patients to help themselves: In the case of heavy alcohol use or poorly controlled diabetes mellitus I tell the patients that they are fortunate in that the key to control of their neuropathy is already in their hands. While this may lead patients to think they are being blamed for their trouble, I never say this. I instead use the opportunity to partner with patients in improving their health. If the etiology is not known, I discuss this candidly and make a plan for a follow-up examination with repeated testing in the future. I take a few minutes to explain the anatomy of neuropathy and emphasize that there is no magic medicine or treatment to help the nerves repair more quickly. This is disappointing for patients but it leads to a discussion of what can be done, whether or not the cause of their neuropathy is known.

When discussing treatment of sensory symptoms, my first question is: “Do you need or want to be treated?” I explain that treatment is for symptoms only and will not help the nerves heal. I also emphasize that there is no treatment for numbness. For some patients, symptoms are mild and they prefer to stay away from medication. Others prefer to control their symptoms with occasional non-steroidal anti-inflammatory medication or over the counter topical treatments such as local anesthetic or capsaicin creams. For patients who are interested in treatments, I categorize these as: non-medication treatments, medications that are not pills and medications that are pills.

Non-medication treatments include use of a warm water vibrating foot bath for 15 minutes before bed. This may calm down the pain long enough to fall asleep. The theory is that the input from large fibers mediating vibration and pressure will block the input from small pain fibers at the level of the spinal cord. Some people get relief from wearing tight socks. Percutaneous nerve stimulation, done by a professional, may relieve pain temporarily, though there is conflicting evidence regarding the usefulness of transcutaneous nerve stimulation. I have been asked about oral and smoked marijuana. There is conflicting data about marijuana’s usefulness for neuropathic pain, while the side effects and legal restriction for both oral and smoked marijuana also complicate the discussion.

Medications that are not pills include local anesthetic applied as a cream, spray, or patch. These are not recommended for people with cardiac arrhythmias or seizures. Capsaicin cream can be effective, but requires three times daily use and is messy. Recent studies show that botulinum toxin injections into the foot may relieve neuropathic pain by blocking the release of Substance p and other factors from sensory nerves.

Oral medications fall into two main categories: anti-seizure and antidepressant. These may be used on- or off-label. The FDA has approved only two medications specifically for this use: pregabalin and duloxetine, however others such as gabapentin, amitriptyline, and nortriptyline are sometimes used. I do not recommend the use of sedatives, such as carisoprodol and methocarbamol, due to their lack of efficacy and potential for addiction.

What if none of these approaches provides relief? The use of opioid medication for neuropathic pain is controversial, and, in my opinion, should be handled by an expert. It is reasonable to refer the patient to a pain management specialist who is comfortable with intravenous pain medications and less frequently used oral agents.

Motor symptoms are less amenable to treatment. I explain to patients that muscles require nerve stimulation to stay healthy and suggest physical and occupational therapy to try to preserve strength, endurance and function.

Autonomic symptoms are sometimes the most serious impediment to the enjoyment of daily life. Orthostatic hypotension can lead to falls and broken bones, daily diarrhea limits socializing and travel, dry mouth can lead to dental decay and erectile dysfunction can lead to depression. Depending on how comfortable you are with the treatment of gastrointestinal, orthostatic, and sexual dysfunction, the neurologist can, at least, initiate treatment and refer to the appropriate specialist.

As with any illness for which there is no satisfactory treatment, neuropathy treatment scams run loose on the Internet. I encourage patients to bring to my attention items they have found online or through patient forums before they buy and use them. While transcutaneous nerve stimulation devices, anodyne light therapy and supplements have hopeful and encouraging descriptions and testimonials, there is no evidence that they are effective in reducing neuropathic pain. In addition, many supplements and vitamins are advertised for the treatment of neuropathic pain. I make it a point to tell my patients that supplements are not regulated by the FDA, therefore consumers have no idea what is actually in the bottle they buy. In addition, supplements may interfere with medications they are taking and may contain filler ingredients, such as ground walnut shells that may trigger allergies.

The Importance of Setting Expectations

As physicians we have certain expectations for the treatment of neuropathy—reducing or alleviating pain and maintaining function. However, patients may have different expectations and these may be greater or lesser than we imagine. When all is said and done, the patient and his family must live every day with the symptoms and disabilities of neuropathy. The most important aspect of the discussion comes after review of the diagnosis, etiology, and treatment. I like to start out by asking what improvements are most important to the patient: Does he seek better mobility and endurance, relief from pain or autonomic symptoms, avoidance of foot complications?

I emphasize what patients can do to feel better. Exercise, regardless of the degree of disability, is important. Some patients require a physical therapy evaluation prior to partaking in exercise due to other health problems but for those who do not require this, keeping active with walking, biking, formal exercise classes, sports (including swimming and dancing) is always worth encouraging. Some patients question whether exercise could further damage the nerves and I tell them that, on the contrary, exercise will not damage nerves and that nerve input to muscle is required to keep muscles healthy. Occupational therapy is useful for those with weakness or sensory loss in the hands and physical therapy with gait training is suggested for those with trouble walking.

I always speak with patients about foot care. In fact, this may be the most important lifestyle issue I address. If they cannot feel their feet, hot water, cuts, a rock in shoe or blister on the heel will not be felt and all can lead to infection. I advise patients to look under and between their toes every day, to keep feet well moisturized, wear proper fitting shoes with socks, not to go barefoot and, most important of all, to not cut their own toenails. I advise filing the nails or seeking professional nail care from a podiatrist or pedicurist. I say, many times a day, “I want you to have all ten toes, all the time.”

Other lifestyle suggestions include limiting alcohol and tobacco use, good blood glucose control, and healthy diet. Some patients argue that it is difficult to give up smoking, while others can be defensive about the quantity of alcohol they drink, but I implore them not to “kick your nerves when they are down.”

After discussing with patients their concerns, I bring up issues they may be thinking about but are not bringing forward. By this time, I have seen the patient a few times and we have gotten comfortable with each other. I can now ask if there are concerns around sexual function and prognosis. It can be a tricky discussion, and I find it best to speak with the patient alone, including the spouse later if the patient requests. Patients with preserved sexual function are often surprised and relieved to hear that neuropathy is no barrier to sexual activity. For those whose function is impaired I offer referral to a urologist. As for prognosis, this depends very much on the cause of neuropathy and I like to use this discussion as an opportunity to encourage patients to undertake lifestyle changes that may not only improve or stabilize their neuropathy but also improve their general health. There often comes the question: “Doctor, will I end up in wheelchair?” Every patient’s circumstance is different and predicating the future is tricky so I like to emphasize what can be done to avoid that fate while still being realistic.

Conclusion: Empowering Patients

Peripheral neuropathy affects many aspects of life. As physicians, we concentrate on diagnosis, treatment of etiology when possible, and treatment of sensory symptoms, but we must not forget to think about day-to-day life from the patient’s point of view. Empowering patients affected by neuropathy to make lifestyle changes that can improve their overall health and make their lives as normal as possible is something we can always do. n

Janice Wiesman, MD, FAAN, is the author of Peripheral Neuropathy: What It Is and What You Can Do To Feel Better, Johns Hopkins Press, 2016.
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