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A burning problem: Small-fiber neuropathy
By
March 12, 2017 02:19
Small-nerve neuropathy, which can result from uncontrolled diabetes and a variety of other disorders, should be prevented or diagnosed and treated early.
Pedicure Jerusalem

Female feet with pedicure. (photo credit:INGIMAGE)

A diagnosis of small-fiber neuropathy (SFN) should literally keep patients on their toes.

Hardly heard of in Israel, it nevertheless affects many tens of thousands of adults here over age 50, and 15 million to 20 million people in the US alone.



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While doctors will try to alleviate the condition that causes SFN, the patient that wants to ameliorate his symptoms would be well advised to run, or at least walk briskly, on a regular basis.

Many patients with SFN have uncontrolled diabetes, even mild diabetes or glucose intolerance (a pre-diabetic state of hyperglycemia), and typically they are overweight, have high blood fat levels (triglycerides). Other patients may have a vitamin B12 deficiency or suffer from hypothyroidism, Sjogren’s syndrome, lupus erythematosus, vasculitis, sarcoidosis, celiac disease, HIV, Fabry disease or fibromyalgia amyloidosis. They also may be taking chemotherapy and even suffering from alcoholism.

In almost half of those with the neuropathy, no cause is found, thus their condition is called idiopathic.

Mostly diabetes – the autoimmune or inflammatory type – causes SFN, which results in unpleasant symptoms due to damage to or loss of small somatic nerve fibers – pain, burning, tingling, or numbness that typically affects the legs. Less commonly, the symptoms also affect other parts of the body including the arms, the oral cavity including teeth, face, hands, chest or trunk.

WHEN DR. Amir Dori – a leading Israeli expert in SFN at Tel Hashomer’s Sheba Medical Center, did a neurology fellowship at Barnes Jewish Children’s Hospital in Missouri, he wasn’t even aware of the spectrum of the condition. But he discovered it while working under his mentor, Prof. Alan Pestronk, a prominent neurologist and director of the neuromuscular division and the neuromuscular clinical laboratory at Washington University School of Medicine in St. Louis.

He went to Missouri after receiving a doctoral degree in morphology at Ben-Gurion University’s Faculty of Health Science in Beersheba and graduated from BGU’s medical school. His internship was at Soroka University Medical Center, while he also completed a post-doctorate in biological chemistry at the Hebrew University of Jerusalem. He was a specialist in neurology at Sheba and at Tel Aviv University.

Dori spoke on small-fiber neuropathy at the recent 13th Annual Update Conference Series on Clinical Neurology and Neurophysiology held at the Crowne Plaza Hotel in Jerusalem.

IN AN interview with The Jerusalem Post, Dori explained that small nerve fibers, or axons, have no myelin (a fatty sheath) on them. Called C fibers, they are located in skin, peripheral nerves and organs and have a small diameter and low speed for conducting electricity. Neuropathy means that these fibers have undergone damage, and their number in any case is reduced as people age.

Symptoms may at first be mild, Dori said, with some patients complaining of vague discomfort in one or both feet similar to the sensation of a sock gathering at the end of a shoe. At a somewhat later stage, patients complain about numbness in their toes, a “wooden” sensation or feeling that they’re walking on sand, pebbles or something as large as golf balls. The most bothersome and fairly typical symptom is burning pain in the feet that extends toward the point of origin or attachment of the limb. The pain often occurs as aching, as pins and needles or an electric shock, he described.

The symptoms of SFN are dependent on the length of the nerves, thus they begin in the longer nerves and progressively attack shorter nerves. This means that most often the symptoms start in the feet and progress upwards, and usually symptoms are more serious in the feet. Many patients also have a widespread condition not dependent on the length of the nerves, called “patchy,” in which the symptoms are more sporadic and can affect many nerves, including the trigeminal nerve responsible for sensations in the face.

About half of diabetics with insulin- dependent type 1 or lifestyle-related type 2 develop neuropathy.

The small fiber type, in addition to innervation of the skin, innervate internal organs and blood vessels and therefore help control autonomic function, including control of blood pressure, bowel movements and ejection of urine from the bladder through the urethra, he said.

“Some diabetics, even when their glucose is not controlled, don’t get neuropathy; we don’t know why.”

The sensory symptoms of small-fiber neuropathy vary a great deal, but the most common are abnormal sensations such as burning, cold, numbness, a feeling of pins and needles; great sensitivity to the feet or other limb; even a light breeze or touch can be painful. Pain leads to lack of sensation. When people with neuropathy are unaware that they have stepped on a sharp object, they can get an injury and even an infection without knowing it.

As a result, they are at risk for ulceration, gangrene and even amputation. Thus diabetics especially are advised never to go barefoot.

When the doctor hears complaints about pain or other sensations of the feet, he should take a complete patient history and examination.

Pain is warning sign that a disease is developing, and the medical problem has to be investigated.”

If the patient suffers from diabetes, the physician should help him to control his blood sugar. If the patient suffers from other neurological symptoms, eye or kidney problems or diarrhea or constipation, treatment of this condition should try to reduce progression of the disease and its symptoms. If an underlying condition is unknown, the doctor should at least try to treat the symptoms.

By contrast, the large nerve fibers, covered with protective myelin, are responsible for motion control, touch, vibration and the sense of the relative position of parts of the body and balance.

Dori noted that the small fibers are about one micron in size and are bundled together, while the large ones are around 10 microns in both males and females. Their shape and bundling are different because of the presence or absence of myelin.

THE PAIN from SFN can cause sleep problems, including restless legs while in bed.

“It really harms the quality of life. Patients are often tired and they can faint due to low blood pressure. It may be difficult to diagnose the neuropathy, as the general practitioner usually finds the physical exam to be normal. An electrical nerve conduction test will usually not detect any abnormality because the electrically detectable large fibers are spared.”

When the doctor can’t reach any conclusions on the cause of symptoms, a tiny skin biopsy can be conducted.

“We at Sheba and neurologists at Wolfson Medical Center in Holon are the only ones to perform skin biopsies to detect SFN. We perform between 20 and 30 skin biopsies per month,” he said.

“We punch a tiny hole in the skin of the heel or the middle of the thigh, just three millimeters in diameter, using a little round knife, first giving a local anesthetic. We then can cut it into slices and observe the tissue under a microscope,” explained Dori.

“We count the number of fibers per millimeter; eight fibers per millimeter in young adults is normal, while two are found in the elderly. If there are fewer than there should be according to the person’s age, we can diagnose SFN.”

“SFN is incurable, but if diagnosed early, it can be alleviated or even reversed,” said the Sheba neurologist.

“We are developing a drug involving the clotting mechanism that prevents neuropathy in mice. We produced diabetes in the rodents, and this drug prevented damage to their small fibers; we used a control group to compare the effects. But we have not reached the clinical stage; testing patients could take about five years.”

DORI STRONGLY urged people with neuropathy to exercise, especially to run, walk briskly or use an elliptical machine.

“It’s so easy today for people to just sit in front of a computer screen or use their cellphone, but being sedentary is very harmful. Exercise improves blood circulation and produces beneficial endorphins [brain hormones that activate the body’s opiate receptors, thus reducing pain]. It produces more growth factors and reduces blood sugar and fats,” he said.

“We have seen that fat mice that run improve their neuropathy. People should do the best they can, but they should exercise often – at least four times a week. My patients say that if they stop exercising for even two days, they again feel some pain that was not there when they ran or walked.”

Education is a major player in promoting health today, said the neurologist.

“The poor and uneducated are more exposed to the risk of illness, because they don’t know how to prevent it and have less access to the best medical care.”

But most SFN patients “don’t accept the fact that they should exercise, even though they get very stressed about what is happening to their bodies. TENS (transcutaneous electrical nerve stimulation) devices may offer some relief; the patient controls a pocket-size box that sends electrical signals to leads placed on affected areas.

Non-steroidal, anti-inflammatory drugs such as aspirin or stronger ones offer very little pain relief for neuropathy. As a result, many patients apply for a license for medical cannabis to alleviate their pain. Some patients get scared and ask me if they’ll suffer from pain all their lives. I tell them, now is the time to change their lifestyle.”
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