Peripheral neuropathy, or
peripheral neuritis, is a disease process that affects the
sensory, reflex, motor and vasomotor (pertaining to the blood vessel)
responses of the peripheral nerves. Some forms of neuropathy affect the motor function of the nerve while other are selective for
sensory function. Peripheral neuropathy can further be broken into subgroups that
define the extent or distribution of the disease;
mononeuropathy- affecting one of the
multiple mononeuropathy- 2 or more
nerves being affected in more than one area
polyneuropathy- multiple nerves affected
at the same time
Causes of peripheral
neuropathy are varied, but trauma is by far the most common cause of
pressure to a peripheral nerve is the cause of some of the more common mononeuropathies
that we know including
anterior tarsal tunnel syndrome and carpal tunnel syndromes.
Particular activities can contribute to direct pressure neuropathies
such as sitting on a wallet (back pocket sciatica), habitual crossing of
the legs (peroneal
palsy), gardening, stooping
or working in jobs with repetitive mechanical duties. Mononeuropathies are very common in foot care and can be the result of
lacing your shoes too tight or wearing shoes that cut into the top of
the foot such as clogs. Direct pressure to the top of the foot can
inhibit normal nerve conduction and result in sensory loss on the top of
the foot and in the toes.
Other forms of trauma that
may contribute to mononeuritis include sprains or dislocations.
The use of power tools, such as routers, saws and jack hammers has been
known to cause single or multiple mononeuritis. Micro-organisms
may cause mononeuritis as seen with conditions such as herpes zoster, or
shingles. TB, leprosy, diptheria and malaria may be other causes
Polyneuropathy may be caused
by a host of conditions. It may be symmetrical or asymmetrical and
may effect the feet, the hands or both the feet and hands together.
conditions - Systemic lupus, scleroderma, sarcoidosis, diabetes or Lyme's Disease
Toxic agents - Chemicals and drugs
include emetine, hexobarbital, barbital, chlorobutanol,
sulfonimides, phenytoin, nitrofurantion, vinca alkyloids, heavy
metals, carbon monoxide, triorthocresylphosphate,
deficiencies and metabolic disorders - Vitamin B deficiency,
malabsorption syndromes, hypothyroidism, porphyria
diabetic peripheral neuropathy.
Peripheral arterial disease (PAD) - advanced PAD results in ischemia
of the peripheral nerves.
Peripheral nerves function by the in-flow
and out-flow of sodium (Na) and potassium (K). As the content of
these two chemicals changes in the nerve, the electric potential shifts
sending an electric charge through the nerve. Any external
influence, such as trauma, diabetes etc, will influence the normal
distribution of charge through the nerve.
The stage of peripheral neuropathy
(including both mononeuropathy and polyneuropathy) can be categorized in three stages;
Stages of peripheral neuropathy
Stage 1- Slight loss of vibratory sensation,
proprioception light touch and sharp/dull differentiation.
Patient may or may not perceive sensory loss. EMG studies
typically negative for change. Onset and duration varies.
Stage 2 - Apparent loss of vibratory
sensation, proprioception light touch and sharp/dull
differentiation. Patient does perceive sensory loss but
does not typically experience severe pain. EMG studies typically positive
for change. Onset and duration varies.
Stage 3 - Advanced loss of vibratory
sensation, proprioception light touch and sharp/dull
differentiation. Patient does perceive sensory loss
and experiences sharp shooting or dull achy severe pain. EMG studies show
advance change. Onset and duration varies.
The onset and duration of peripheral
neuropathy varies in each individual case. As an example, the onset,
severity and duration of peripheral neuropathy secondary to diabetes
would vary based upon many factors including fluctuations in blood sugar
levels and how compliant the patient
has been over the course of treatment for their disease. In cases of
peripheral neuropathy, similar variables apply such as the severity of
the injury, the duration of injury prior to seeking care, etc.
Neurological testing for peripheral
neuropathy may include testing for the ability to sense vibration,
differentiation between warm and cold, differentiation between sharp and
dull touch and the ability to tell where one is in space
(proprioception). A Semmes Weinstein monofilament testing device
is a common tool used today. This tool looks like a ball point
pen and contains a 5mil monofilament wire. The monofilament wire
is touched to the skin to determine the amount of sensory loss.
Individuals with peripheral neuropathy will loose the ability to sense
the touch of the monofilament wire.
EMG (electromyelogram) studies help to
quantify the degree of neuropathy and can be used to establish a base
line or monitor change in the progression of peripheral
neuropathy. This test uses an electrical signal which is sent
along the course of the nerve and timed. When compared to normal
values, any variation, such as delay in the normal conduction rate may
indication a form of damage that the peripheral nerve has sustained.
Treatment of mononeuropathy and multiple
The first step in treating mononeuropathy and multiple
mononeuropathy is attempting to identify a source of entrapment. A
thorough history and physical exam by your doctor should include evaluation of
lumbar disc disease, back and leg pain and focal evaluation of specific
peripheral nerves. It's important to evaluate peripheral nerves from their
origin in the spine to the site of pain.
Focal entrapment of peripheral nerves is common. Entrapment
can be caused by adjacent tissue structures that impinge upon the nerve.
Impingement can be caused by normal anatomy including ligaments, veins or
muscles. Soft tissue tumors such as a ganglionic cyst are a common reason
for impingement of a peripheral nerve in an enclosed space. Varicose veins
and soft tissue tumors can also be a contributing factor in tarsal tunnel
syndrome. If soft tissue tumors or varicosities are suspected, these
tumors should be removed. Removal of the tumor should be performed in
conjunction with a peripheral nerve release.
Painful mononeuropathy can be treated with several methods that
focus on the destruction of the contents of the nerve. Destruction of the
nerve contents is accomplished by a technique called neuroablation.
Neuroablation can be performed in a number of ways. These methods include
chemical ablation, radiofrequency ablation or cryoablation. The most
common method of chemical ablation employes 4% absolute alcohol. A series
of 5-7 injections are performed over a period of time, separated by 1 week
intervals. Radiofrequency neuroablation and cryoablation are typically
performed in a surgical center of hospital on an outpatient basis.
Transection and transposition of painful mononeuritis is uncommon.
Transection and transposition is performed in cases of reclacitrant pain.
The individual nerve that is contributing to mononeuritis is cut and transposed
into living tissue. This tissue is typically muscle or bone.
Transposition is used to inhibit the growth of stump neuromas following
transection. The following images show transection of the sural nerve with
transposition of the nerve into the soleal muscle of the lower leg. This
procedure was performed for recalcitrant pain of the lateral foot following a
Treatment of polyneuropathy
single most important step to be taken in the treatment of peripheral
neuropathy is the identification and elimination of the primary cause of the
neuropathy. For instance, in diabetes, the single most important issue
affecting DPN is serum glucose levels. Controlling the onset of
DPN is best managed by decreasing serum blood sugar levels. Once the primary contributing factors are removed, the
nerve may have an opportunity to regenerate. Supportive efforts
are helpful during this phase of repair and include nutritional support
and the use of anti-oxidants. The following are some of the supportive
measures that can be used in stages 1-3 of peripheral neuropathy;
(B6) has been used for years as a method of nutritional support
following peripheral nerve damage. Vitamin B6 is water soluble and
can therefore be eliminated by your body. Common doses range as
high as 250mg/day.
Exciting new treatment
modalities for peripheral neuropathy includes the used of
anti-oxidants. These scavengers of the body are used to eliminate
toxins which may contribute to peripheral neuropathy.
Anti-oxidants used to treat peripheral neuropathy include gamma-linoleic
acid and alpha lipoic acid (thiotic acid). Alpha lipoic acid
increases glucose uptake in muscle and fat cells to improve both the
symptoms of DPN and diabetes. It has also been suggested the alpha
lipoic acid may help treat insulin resistance. A study by Tankova
et al. showed up to a 65% reduction in the symptoms of DPN with high
doses of alpha lipoic acid.
Other treatment may include
the use of metabolic factors or medications such as aldose reductase
inhibitors or aminogunidine. Autoimmune therapies and nerve growth
factors have also been tried. Oral dextromethorphan, a
N-methyl-D-aspartate (NMDA) receptor antagonist has also been used for
chronic peripheral neuritis. Dextromethorphan is widely available
over the counter in non-narcotic cough preparations such as RobitussinDM
and Benylin DM. It is believed that dextromethorphan has the
chemical ability to relieve peripheral neuritis pain by blocking pain
sensation. Studies have shown as much as a 24% reduction in
peripheral neuritis pain as compared to a placebo. Typical dosing
for these tests were 120mg/day or 3 tsp. every six hours with some
ranging up to 3 tbsp every six hours.
Mentanx is a prescription medical food supplement that is
used for dietary management of endothelia dysfunction in patients with
diabetic peripheral neuropathy. Mentanx increases nitric oxide
synthesis and offers the potential advantage of improving blood flow to
peripheral nerves. The literature shows an increase of 136% blood
flow to the peripheral nerves with the use of Mentanx over 8 weeks.
Mentanx is only approved for diabetic peripheral neuropathy.
The success of each of the modalities mentioned above can
be monitored with the use of periodic epidermal small nerve biopsies.
The epidermal small nerve biopsies can be performed in a matter of
minutes in your doctor's office using just a local anesthetic.
Small never fiber biopsies are used to quantify nerve fiber counts.
An increase in small nerve fiber counts over time indicate a positive
response to the treatment modalities mentioned above.
Stage 3 peripheral
neuropathy symptoms often produce severe pain. These symptoms are
described as electrical sharp shooting pains, burning pain and tingling
pain. These symptoms are tolerable during the day (for most
patients) but become severe at night often limiting the normal sleep
cycle. Neurontin (gabapentin) is a medication frequently used to suppress the
symptoms of peripheral neuropathy. Neurontin was originally
developed to control seizure disorders such as epilepsy. Neurontin
can be taken in divided doses during the day or in a single does at
bedtime. It is best to titrate Neurontin based upon the degree of
symptoms. Normal daily doses range from 300mg to
2400mg. Although the use of Neurontin for the control of symptoms
due to neuropathy is considered an 'off-label' use by The Food And Drug
Administration, doctors use it regularly for control of symptoms.
Cymbalta (duloxetine hydrocholride) was recently
introduced by Eli Lilly Co. Cymbalta is a selective serotonin and
norepinephrine reuptake inhibitor (SSNRI) used for the treatment of pain and
depression associated with diabetic peripheral neuropathy. Cymbalta is FDA
approved for control of the symptoms of DPN. Cymbalta has been found in
studies to be safe and effective. Dosage for Cymbalta is usually between
60-120 mg daily.
Lyrica (pregabalin) is a new generation of
gabapentin introduced by Pfizer in 2004. Lyrica is also approved by The
FDA for the treatment of symptoms secondary to DPN. The exact mechanism of
action is not fully understood, but the presumed action is that pregabalin binds
with the alpha2-delta subunit of protein of calcium chanels and acts to reduce
the release of excitatory neurotransmitters. Lyrica also has been shown in
clinical testing to be safe and effective.
Other medications for stage
3 symptoms include antidepressants such as Elavil. One of the side
effects of Elavil and its' related family of medications is
drowsiness. This side effect can be helpful in restoring the
normal sleep cycle in patients who suffer from painful peripheral
Topical medications that can be used to sooth the pain of
peripheral neuropathy found in stage 3 include