Small nerve fibers defy neuropathy conventions

April 11, 2016
Healthy small nerve fibers. Credit: Michael Polydefkis

Results of a small study of people with tingling pain in their hands and feet have added to evidence that so-called prediabetes is more damaging to motor nerves than once believed, in a report on the study published online in JAMA Neurology on April 11.

Johns Hopkins neurologists say the study of patients with small fiber neuropathy showed unexpected deterioration over the entire length of sensory , rather than just at the longest ends first, which the investigators say defies the conventional wisdom of how nerves were thought to deteriorate.

Over the three-year course of the study of the 62 participants, 13 of them with prediabetes, the investigators found that generalized damage occurs in those with prediabetes, and that the precursor condition may be less benign than most clinicians appreciate.

"I liken small fiber neuropathy to the canary in the coal mine," says senior author Michael Polydefkis, M.D., professor of neurology at the Johns Hopkins University School of Medicine and director of the Cutaneous Nerve Lab. "It signals the beginning of nerve deterioration that with time involves other types of nerve fibers and becomes more apparent and dramatically affects people's quality of life. The results of this new study add urgency to the need for more screening of those with the condition and faster intervention."

Small diameter nerve fibers reach out to the surface of the skin, and their damage is often marked by development of burning pain in the feet. But routine nerve tests, like nerve conduction, and routine examinations often fail to identify nerve damage because those measurements mostly assess injury to large diameter nerve fibers. The most common cause of small fiber neuropathy is diabetes, Polydefkis notes, but it can also be caused by lupus, HIV, Lyme disease, celiac disease or alcoholism.

In an effort to measure damage more accurately in small nerve fibers in people with small fiber neuropathy symptoms, Polydefkis and his team took small samples of skin—the size of a large freckle—from 52 patients diagnosed with small fiber neuropathy and from 10 healthy controls. Of the 52 patients enrolled in the study with small fiber neuropathy, 13 were considered to have prediabetes, 14 had type 2 diabetes, and 25 had normal blood sugar and an unknown cause of neuropathy. The participants ranged in age from their mid-40s to late 60s, and just less than half were female. Skin samples were taken from the ankle, the lower thigh near the knee and the upper thigh. Three years later, samples from the same area in the same group were taken for comparison.

Damaged small nerve fibers. Credit: Michael Polydefkis

Microscopic analysis of the skin samples was done to determine the density of small nerve fibers over time. According to the lead author of the study, Mohammad Khoshnoodi, M.D., assistant professor of neurology at Johns Hopkins, a lower density of fibers indicates more nerve damage.

Initially, he says, all patients with small fiber neuropathy had fewer nerve fibers at the test site on the ankle compared to the upper thigh, demonstrating more the further down the leg measured. After three years, all three groups of those with small fiber neuropathy lost nerve fibers at the site tested in the ankle. But what surprised the researchers was that nerve fibers were lost at similar rates from the lower and upper thigh sites as well, a phenomenon that would not have been expected if the longest nerve fibers were the most vulnerable.

"We are all taught in medical school that the longest nerves degrade first, and we show that this isn't always the case," says Khoshnoodi.

Patients with prediabetes or diabetes had at least 50 percent fewer small nerve fibers in their ankles initially than those participants with an unknown cause for their small fiber neuropathy, indicating these patients started the study with more damage to their small nerve fibers.

The patients with prediabetes continued to have worsening damage to their small nerve fibers over the course of the study; they lost about 10 percent of their nerve fiber density each year at all sites tested along the leg. Patients with diabetes also lost similar rates of nerve fibers along the three sites of the leg.

"I expected that people with diabetes would do worse, but I didn't really expect people with prediabetes to experience a similar rate of degradation of their small nerve fibers," says Polydefkis.

Khoshnoodi cautions that the study was small, and that other factors in addition to high blood sugar, such as smoking, high blood pressure and high cholesterol, may also have contributed to the decline. Future studies that address these risk factors will need to be performed to determine if prediabetes is as debilitating to nerves as full-blown diabetes.

According to the National Institute of Neurological Disorders and Stroke, an estimated 20 million people in the U.S. have some form of peripheral neuropathy. About 50 percent of people with diabetes have neuropathy.

Explore further: New research sets stage for noninvasive monitoring of HIV-induced peripheral neuropathy

Related Stories

New research sets stage for noninvasive monitoring of HIV-induced peripheral neuropathy

May 12, 2014
Corneal nerve fiber assessment has great potential as a tool to diagnose and monitor peripheral neuropathy induced by HIV, say scientists at the Johns Hopkins University School of Medicine. The results of their study are ...

YouTube videos on peripheral nerve pain may misguide patients

October 21, 2015
Researchers who combed YouTube for videos regarding peripheral neuropathy, or nerve damage that causes weakness, numbness, and pain in the hands and feet, found 200 videos, but only about half of them were from healthcare ...

To fix diabetic nerve damage, blood vessels and support cells may be the real targets of treatment

June 23, 2011
Blood vessels and supporting cells appear to be pivotal partners in repairing nerves ravaged by diabetic neuropathy, and nurturing their partnership with nerve cells might make the difference between success and failure in ...

Researchers uncover source of mystery pain

June 22, 2011
An estimated 20 million people in the United States suffer from peripheral neuropathy, marked by the degeneration of nerves and in some cases severe pain. There is no good treatment for the disorder and doctors can find no ...

Study finds nerve damage after hip surgery may be due to inflammation

May 5, 2014
A recent Mayo Clinic Proceedings article links some nerve damage after hip surgery to inflammatory neuropathy. Historically, nerve damage from hip surgery has been attributed to mechanical factors caused by anesthesiologists ...

Prediabetes may not explain diabetic polyneuropathies

February 22, 2012
In a reversal of two decades of medical reports, a Mayo Clinic study finds the frequency of nerve damage called diabetic polyneuropathy is similar in prediabetic patients and healthy people. Physicians should seek explanations ...

Recommended for you

Now you like it, now you don't: Brain stimulation can change how much we enjoy and value music

November 20, 2017
Enjoyment of music is considered a subjective experience; what one person finds gratifying, another may find irritating. Music theorists have long emphasized that although musical taste is relative, our enjoyment of music, ...

MRI uncovers brain abnormalities in people with depression and anxiety

November 20, 2017
Researchers using MRI have discovered a common pattern of structural abnormalities in the brains of people with depression and social anxiety, according to a study presented being next week at the annual meeting of the Radiological ...

Deletion of a stem cell factor promotes TBI recovery in mice

November 20, 2017
UT Southwestern molecular biologists today report the unexpected finding that selectively deleting a stem cell transcription factor in adult mice promotes recovery after traumatic brain injury (TBI).

Brain cell advance brings hope for Creutzfeldt-Jakob disease

November 20, 2017
Scientists have developed a new system to study Creutzfeldt-Jakob disease in the laboratory, paving the way for research to find treatments for the fatal brain disorder.

Neuroscience research provides evidence the brain is strobing, not constant

November 17, 2017
It's not just our eyes that play tricks on us, but our ears. That's the finding of a landmark Australian-Italian collaboration that provides new evidence that oscillations, or 'strobes', are a general feature of human perception.

Brain activity buffers against worsening anxiety

November 17, 2017
Boosting activity in brain areas related to thinking and problem-solving may also buffer against worsening anxiety, suggests a new study by Duke University researchers.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.