(mentions CMT) A Pain-Free Window Into Painful Neuropathies

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A Pain-Free Window Into Painful Neuropathies

http://www.urmc.rochester.edu/pr/news/story.cfm?id=1750

Scientists have demonstrated a new technique for detecting a painful

nerve condition known as neuropathy, which affects millions of people

with diabetes and many other patients as well.

The painless technique focuses on tiny structures in the skin known

as Meissner corpuscles, which encapsulate the endings of microscopic

nerves in our hands, feet, and other areas. When someone tickles your

feet, or lightly brushes the palm of your hand, or gives you a kiss –

it's Meissner corpuscles that are detecting the touch. The tiny

structures act like little sensors, allowing us to feel light touch

and pressure.

Now a neurologist at the University of Rochester Medical Center,

working together with scientists from Lucid Technologies in

Rochester, N.Y., has demonstrated a new way to monitor the

structures, which offer a direct window into a condition known as

peripheral neuropathy. The team showed that reflectance confocal

microscopy, a technology for looking just beneath the surface of the

skin, can be used to see and count the number of the structures in a

person's fingers and hands. The work gives doctors a non-invasive way

to detect and monitor the progression of nerve damage in patients.

The research appears in the December 4 issue of the journal Neurology.

Doctors have known that the number and density of Meissner corpuscles

in a person's hands and feet offer a snapshot into the degree of a

patient's nerve damage. As nerves degenerate and die, the corpuscles

disappear. The difficulty has been actually visualizing and counting

them.

Currently, doctors take a small biopsy of the skin, freeze and stain

the tissue, and then count the structures. Neurologist

Herrmann, MBBCh, the lead author of the Neurology paper, helped

develop and popularize skin biopsy about 10 years ago as a way to

keep close track of the condition of nerves in patients. At the time,

for some forms of peripheral neuropathy, it was a big improvement

over previous methods, which required a much larger biopsy of a large

nerve.

Even so, " Taking a small piece of skin is not ideal, " said Herrmann,

associate professor of Neurology and of Pathology and Laboratory

Medicine. " It can be painful for the patient; the processing can be

time-consuming; and it's impossible to measure the exact same area of

skin year to year to track the progression of the disease. "

A few years ago Herrmann met a scientist from Lucid, a medical device

and information company that is creating tools for physicians based

on innovative technologies such as confocal microscopy. The

technology uses light to actually look beyond the surface of skin

tissue into the layers of skin below. The technology is being used

more and more to track skin cancers and to look at tissue samples in

the operating room.

Herrmann and the Lucid team began a study of some of the tiniest

nerves in our body, those that reach into the furthest reaches of our

hands and feet. Damage to those nerves leads to a variety of

troublesome symptoms for the millions of Americans who have some type

of peripheral neuropathy. Symptoms in the feet and hands can include

numbness, burning, tingling, weakness, and pain.

While diabetes is the most common cause of neuropathy, it's caused by

a variety of other conditions as well. Patients with HIV are prone to

getting it. Excess alcohol consumption can bring it on, as can some

vitamin deficiencies, cancer treatments, and dozens of inherited

disorders, most notably Charcot-Marie-Tooth disease.

" These patients are often dismissed, and many really suffer, " said

Herrmann. " Diagnosis is often difficult. The small nerves in the skin

are basically invisible to standard techniques for checking the

function of a person's nerves, such as conduction tests. "

So Herrmann lined up 15 little pinkies – well, 15 research subjects

willing to put their little pinkies under the microscope. The group

included 10 healthy people, and five who had neuropathies from

various causes, such as diabetes or HIV.

The researchers found, as expected, that the healthy volunteers had

many more Meissner corpuscles in the tip of the pinkie finger – about

12 such structures per square millimeter, compared to a mean of 2.8

in people with neuropathy. Patients with neuropathy also had fewer of

the structures at the base of the thumb.

While the results were not surprising, attaining them so easily was.

Volunteers simply held their pinkie finger under a microscope for a

few minutes. No pain, no blood, no tissue preparation.

In an editorial about the research, J. Dyck, M.D., of the Mayo

Clinic wrote in the journal, " The approach may find use as the gold

standard of tactile sensation and of large fiber sensorimotor

polyneuropathy. " But he also pointed out some limitations of the

work. Dyck said the technique needs to be tested in greater numbers

of people, pointed out that the equipment needed for reflectance

confocal microscopy is expensive, and mentioned the need to

differentiate between healthy and abnormal Meissner corpuscles.

An advance in screening would be appreciated by millions of patients.

More than half of people with diabetes will eventually develop

neuropathy. Most of them won't feel pain – they'll simply lose

sensation in their feet, making them vulnerable to wounds that can

result in severe infections. Oftentimes sensation slips away so

gradually that patients don't even notice. A new screening tool would

help doctors monitor patients more closely so that both they and

patients are aware of nerve damage and can do everything they can to

prevent further damage.

" Neuropathy is very difficult to treat, and part of the reason is

that currently, we usually identify it too late, after there has been

significant damage, " said Herrmann, director of the Peripheral

Neuropathy Clinic at Strong Memorial Hospital. " Treatments might be

more beneficial if we could detect the condition earlier.

" The idea is to move from an invasive biopsy for monitoring nerve

endings, to non-invasive, painless approaches. A person could have

this technique done as frequently as is necessary, for instance.

That's an attractive notion for tracking the condition of nerves in

patients, " said Herrmann, who is now assessing the technique in 75

people, with funding from the National Institute of Neurological

Disorders and Stroke.

In addition to Herrmann, authors of the paper from Lucid were

pathologist J. Neil Boger, M.D.; Christi Alessi-Fox; and Cortney

Jansen, who began work on the project when she was an undergraduate

biomedical engineering major at the University of Rochester.