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 peripheral nerves
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 mononeuropathy. Direct pressure to a peripheral nerve is the cause of some of the more common mononeuropathies that we know including tarsal tunnel syndrome, 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), 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.

Tumor growth or thinning of common body portals (such as the spine) may also be a cause for pressure neuropathy. Tarsal tunnel syndrome can occasionally be cause by tumor growth within the confined areas of the medial ankle.

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 of mononeuritis.

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.

Causes of polyneuropathy

Collagen vascular 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, orthodinitrophenol

Nutritional deficiencies and metabolic disorders - Vitamin B deficiency, malabsorption syndromes, hypothyroidism, porphyria

Peripheral neuropathy, whether single (mono) or multiple (poly) neuropathy can, in many cases, be very similar in onset. As a result, the methods of diagnosing these related conditions are similar.

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 degree 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 with each condition. As an example, the onset, severity and duration of peripheral neuropathy secondary to diabetes would vary based upon many factors including the duration of time until blood sugars were adequately controlled and how compliant the patient has been over the course of treatment for their disease. In cases of traumatically induced 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.

Two new tools have been introduced in the past ten years that are more more able to determine the degree of sensory loss due to peripheral neuropathy. The VPT meter (vibratory perception threshold) manufactured by Xalis Medical, Inc. Compared to the Semmes Weinstein device, this tool brings a new sensitivity and specificity to testing vibratory sensation. Also, the PSSD testing device produced by Sensory Management Service, is quite capable of differentiating degrees of sensory neuropathic change.

Diabetic peripheral neuropathy

18.2 million people living in the United States are diabetics (6.3% of the population). Diabetic peripheral neuropathy (DPN) is a common complication of diabetes. Diabetic peripheral neuropathy is a complication that can be expected in 60-70% of all cases of diabetes mellitus (DM). Many cases of diabetic peripheral neuropathy may remain sub-clinical but will show signs of change on nerve conduction testing (EMG). Patients with peripheral neuropathy should always be questioned regarding a personal or family history of DM.

In DM, the long term exposure of the peripheral nerves to elevated blood sugar levels and associated blood borne toxins results in the erosion of the peripheral nerve sheath making the nerve more sensitive to caustic body fluids. Many theories have been proposed to detail how long standing DM effects the peripheral nerves. The most accepted theory that has been proposed relates to elevated levels of sorbitol. Sorbital is a by-product of the metabolism of glucose. Impaired metabolism of glucose results in elevated levels of sorbital which is known to be toxic to the peripheral nerves. As a general rule, peripheral neuropathy is known to be caused by long term exposure to caustic chemical such as alcohol in alcoholic peripheral neuropathy . Long term exposure to sorbital appears to be a very similar mechanism for the onset of peripheral neuropathy.

The symptoms of diabetic neuropathy are described as a 'stocking and glove' distribution, meaning that the symptoms affect the foot, leg and hand. Symptoms begin distally and progress proximally over time. The symptoms are described as a burning sensation and electrical shock sensation that becomes worse at night or when a patient is not on their feet.

Diabetics with advanced peripheral neuropathy also experience a loss of proprioception, or the ability to determine where you are in relationship to the ground or space. As a result, diabetics with peripheral neuropathy tend to feel unstable on their feet. Falls are common which can result in additional morbidity such as broken hips.

Treatment of ideopathic neuropathy and diabetic peripheral neuropathy

The 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;

Pyridoxine (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.

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 neuropathy symptoms.

Topical medications that can be used to sooth the pain of peripheral neuropathy found in stage 3 include Biofreeze and Neuragen PN.

No information is available for this topic.

The peripheral nervous system includes the sensory (touch) and motor components (muscle action) of the cranial and spinal nerves as well as the autonomic nervous system, with its sympathetic and parasympathetic divisions. The peripheral nervous system serves as a conduit, carrying sensory information to the central nervous system and motor commands out to the peripheral effector organs such as muscle.

Peripheral nerves are composed of individual axons surrounded by connective tissue and fibroblasts (endoneurium). Groups of nerve fibers form fascicles, which are in a continual state of rearrangement. Each fascicle is surrounded by connective tissue and rings of flattened cells (the perineurium) and groups of fascicles by epineurium. A fascicle contains individual axons of various sizes. Axons greater than 2 microns in diameter are surrounded by myelin sheaths, which are produced by Schwann cells and are arranged in a series of segments by the nodes of Ranvier. As already mentioned, each segment is formed by only one Schwann cell and a single Schwann cell can myelinate only one segment of a single axon. The larger the diameter of an axon, the thicker the myelin sheath.

No information is available for this topic.

The symptoms of peripheral neuropathy vary with the primary reason why the neuropathy has occurred. For instance, in cases of chemical toxicity, the amount of chemical exposure, the duration of exposure, the general health of the patient (such as overall liver function) and the nature of treatment all become variables in the outcome.

In cases of diabetic peripheral neuropathy, the extent of damage and degenerative change of the nerve is greatly due to the control of blood sugar levels over months to years.  The earlier that your diabetes is addressed and controlled, the less the chance for onset of diabetic peripheral neuropathy.  When necessary, switching from oral medication to insulin is an important and helpful step in preventing the onset of diabetic peripheral neuropathy.

Peripheral neuropathy is often a symptom of other diseases including;

Collagen vascular 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, orthodinitrophenol. Excessive alcohol intake is a common toxic agent.

Nutritional deficiencies and metabolic disorders - Vitamin B deficiency, malabsorption syndromes, hypothyroidism, porphyria

Other conditions to consider when evaluating peripheral neuropathy include multiple myeloma, multiple sclerosis, ALS, TIA (transient ischemic attacks) or CVA cerebral vascular accident (stroke). Many other neurological conditions present with symptoms of peripheral neuropathy, therefore, when dealing with the symptoms of peripheral neuropathy it is always advisable to seek the help of a healthcare provider trained in this area.

• Diabetic Foot Care

• Complex Regional Pain Syndromes

• Mortons Neuroma

• Tarsal Tunnel Syndrome

This article was written by Jeffrey A. Oster, DPM and last updated 1/24/08.  Additional references include;

Pathologic Basis of Disease, 2dn Edition. W.B. Saunders Company, 1979

The Merk Manual, 15th Edition. Merk, Sharp and Dohme Research Laboritories, 1987

Mueller, M.J. Identifying patients with diabetes mellitus who are at risk for lower extremity complications: Use of the Semmes-Weinstein monofilaments. Phys. Ther. 76:68-71, 1996

Apelqvist J, Larsson J, Agardh CD: The influence of external precipitating factors and peripheral neuropathy on the development and outcome of diabetic foot ulcers. J Diabetes Complications 4: 21, 1990

Melton LJ, Dyck PJ. Clinical features of diabetic neuropathies:Epidemiology. In: Dyck PJ, Thomas PK, Asbury AK, et al (eds). Diabetic Neuropathy. Philadelphia, PA: WB Saunders, 1987:27-35

Brown MJ, Asbury AK. Diabetic Neuropathy. Ann Neurol 1984:15;2-12

Feldman EL, Stevens MJ, Thomas PK, et al. A practical two-step quantitative clinical and electrophysiological assessment for the diagnosis and staging of diabetic neuropathy. Diabetes Care 1994;17:1281-9

Keen H, Payan J, Allawi J, et al. Treatment of diabetic neuropathy with gamma-linoleic acid. The Gamma-linoleic Acid Multicenter Trial Group. Diabetes Care 1993;16(1):8-15

Wu S, Armstrong DG. Pharmacological management of diabetic neuropathy: and evaluation. Podiatry Management 11/2005. Pages 159-165.

Tankova T, Cherninkova S, Koev D. Treatment of diabetic mononeuropathy with alpha lipoic acid. Int J Clin Pract. Jun 2005;59(6):645-650.