What is neuropathy?
Neuropathy is any disease or disorder that affects the functioning of nerves in a person’s body. The nervous system is divided into two parts: the central nervous system (CNS), which includes the brain and spinal cord, and the peripheral nervous system, which branches off the brain stem and spinal cord to the rest of the body. The peripheral nervous system is further subdivided into the somatic and autonomic nervous systems. The…
Neuropathy is any disease or disorder that affects the functioning of nerves in a person’s body. The nervous system is divided into two parts: the central nervous system (CNS), which includes the brain and spinal cord, and the peripheral nervous system, which branches off the brain stem and spinal cord to the rest of the body. The peripheral nervous system is further subdivided into the somatic and autonomic nervous systems. The somatic nervous system controls sensation and movement, while the autonomic nervous system controls vital functions, such as heart rate and breathing.
Nerve cells originate in the central nervous system and have long fibers that extend throughout the body and terminate as nerve endings in skin, muscle, and organs. These cells transmit impulses from the brain and spinal cord to other parts of the body.
- Sensory nerves relay information about temperature, pressure, vibration, pain, and muscle position from various locations in the body (such as the tip of an index finger) to the brain.
- The brain processes impulses received from sensory nerves and also sends commands to muscle groups through motor nerves, allowing a person, for example, to walk, sit, run, and grasp objects.
- Autonomic nerves send and receive messages that affect internal organs and involuntary functions, such as regulating blood pressure and heart rate, breathing, and digestion.
Neuropathy can develop in a wide variety of diseases and conditions. It may be inherited or acquired, acute or chronic, temporary or permanent. Nerve damage may occur in a single location or may be widespread. It may primarily affect sensory nerves, motor nerves, autonomic nerves, or multiple types. Anything that damages nerves can interfere with their ability to transmit accurate signals, which can lead to a number of signs and symptoms.
While neuropathy can affect both the central and peripheral nervous systems, this article will focus mostly on peripheral neuropathy, with some discussion of autonomic neuropathy. In the U.S., it is estimated that 20 million people have some form of peripheral neuropathy.
According to the National Institute of Neurological Disorders and Stroke (NINDS), more than 100 types of peripheral neuropathy have been identified. When the cause is unknown, it is referred to as idiopathic neuropathy; about 23% of cases are classified as such.
Examples of common causes of peripheral neuropathy include:
- Trauma – Physical injury to nerves is the most common cause of neuropathy. In addition to acute nerve injury resulting from falls, motor vehicle accidents, sports injuries, or surgery, peripheral neuropathy may be the result of repetitive stress or any condition that traps, compresses, or damages a nerve (e.g., carpal tunnel syndrome).
- Diabetes – 60% to 70% of people with diabetes will develop some form of nerve damage, a condition called diabetic neuropathy.
- Medications, especially certain chemotherapy agents, but also some antiretroviral agents used to treat HIV infection, anticonvulsant drugs, and heart and blood pressure medications, can damage nerves and cause neuropathy.
- Nutritional and vitamin deficiencies – Vitamin B12 deficiency damages the myelin sheath that surrounds and protects nerves. Without this protection, nerves cannot function properly. Other B vitamin deficiencies such as B1, B6, and B3 can cause neuropathy as can vitamin E and niacin deficiencies.
- Alcoholism – Long-term alcohol abuse causes nerve damage that may not be reversible, even if a person stops drinking. People who abuse alcohol may also develop nutritional and dietary deficiencies that can contribute to neuropathy.
Examples of other causes include:
- Kidney, liver and lung disease, or other critical illness
- Hypothyroidism and pituitary disorders
- Autoimmune disorders such as Guillain-Barré syndrome, rheumatoid arthritis, and lupus
- Benign or cancerous tumors that exert pressure on nerves
- A wide range of infections, including herpes simplex virus (HSV), shingles (varicella zoster virus), Lyme disease, HIV/AIDS, cytomegalovirus (CMV), Epstein-Barr virus, syphilis, leprosy, diphtheria, and parasites
- Exposure to environmental and industrial toxins, such as lead, arsenic, and mercury, some pesticides and industrial solvents
- Monoclonal gammopathy
- Paraneoplastic syndrome (i.e., cancer-associated)
Signs and Symptoms
The symptoms of neuropathy depend upon the type of nerve(s)—sensory, motor, or autonomic—affected.
Symptoms of peripheral neuropathy typically start with numbness, prickling, or tingling in the toes or fingers. These sensations may spread to the feet or hands and cause burning, freezing, throbbing, and/or shooting pain that is often worse at night. The pain may be constant or may come and go. The onset of neuropathy may be sudden or it may develop gradually.
- Muscle weakness, cramping, and/or twitching
- Muscle wasting (atrophy)
- Loss of reflexes
Sensory nerve damage can cause the following symptoms:
- A sensation or wearing invisible gloves or socks
- Loss of reflexes and “position sense,” which affects coordination and balance
- Extreme sensitivity to touch, even with very light pressure (such as from a bed sheet)
- Decreased ability to detect touch, pressure, temperature, and vibration
If autonomic nerves are affected, signs and symptoms may include:
- Blurred vision; slow pupil reaction, which affects night vision
- Decreased or excessive sweating and heat intolerance
- Difficulty swallowing or breathing
- Dizziness and fainting when standing due to low blood pressure
- Erectile dysfunction in males; vaginal dryness in females
- Heart rate that does not change appropriately with exercise
- Incontinence and difficulty urinating and emptying the bladder
- Lack of awareness of low blood glucose
- Altered movement of food through the gastrointestinal tract, leading to constipation or diarrhea, abdominal pressure and bloating, nausea, heartburn
Complications of peripheral neuropathy are typically the result of sensation loss, which makes a person less likely to feel the discomfort caused by trauma, burns, or pressure until tissue damage has already occurred. People with peripheral neuropathy are prone to:
- Skin burns and pressure sores
- Infection – Sores that develop may be slow to heal and can become infected. This can lead to tissue erosion, scarring, and, in some cases, the need for amputation.
- Falls – Decreased muscle control and loss of balance and coordination can lead to tripping and falling.
Autonomic neuropathy can cause organ dysfunction, irregular heart rhythms, breathing difficulties, urinary tract infections, bowel problems, and sexual dysfunction.
The goals of testing are:
- To diagnose the presence of neuropathy and distinguish it from other conditions that may cause similar symptoms
- Identify the cause of neuropathy, where possible
- Evaluate the location, extent, and severity of the nerve damage and assess organ function
- Identify underlying conditions that make neuropathy worse
- Detect and evaluate complications
The diagnostic workup for neuropathy begins with a thorough medical history and physical exam.
- The medical history may include questions about symptoms, work environment, lifestyle habits, exposure to toxins, alcohol use, risk of HIV or other infectious diseases, and family history of neurological diseases.
- The physical exam is likely to include a neurological exam to check tendon reflexes, muscle strength and tone, and the ability to sense vibration, light touch, body position, temperature, and pain.
Depending on the results of the medical history and physical/neurological exam, one or more of the following tests may be ordered:
- Nerve conduction tests – to evaluate nerve transmission and measure the degree of damage in large nerve fibers (both sensory and motor)
- Electromyography (EMG) – to detect abnormal electrical activity in muscles and help differentiate between muscle and nerve disorders
- Other nerve function tests – may include tests to record autonomic nerve function, a sweat test, and tests that record the ability to sense touch, vibration, cooling, and heat
- Nerve biopsy – to evaluate damage to nerve fibers
- Skin biopsy – to determine the number of nerve endings present and identify damage in small nerve fibers
Imaging tests, such as computed tomography (CT) scans or magnetic resonance imaging (MRI), may be performed to identify tumors, herniated discs, or other abnormalities that could be exerting pressure on nerves and causing neuropathy. See RadiologyInfo.org for more information about imaging tests.
If autonomic nerve involvement is suspected, additional testing may be performed to evaluate heart rate, blood pressure, the digestive tract, pupil response, and sweating.
Laboratory testing is used to look for underlying conditions that may cause or contribute to a neuropathy, detect complications, and evaluate organ function. Testing may include:
- Blood glucose – to detect diabetes and evaluate glucose control
- Comprehensive metabolic panel (CMP) – to evaluate liver, kidney, and other organ function; to detect metabolic problems
- Vitamin B12 – and other vitamin tests as indicated to detect vitamin deficiencies
- Thyroid panel – to detect hypothyroidism
- Cerebrospinal fluid (CSF) analysis – to detect abnormalities or infections in the central nervous system
- Specific tests for autoimmune disorders, such as antinuclear antibody (ANA)
- Specific tests for infectious conditions, such as shingles (varicella zoster virus), Lyme disease, HIV/AIDS, cytomegalovirus (CMV), Epstein-Barr virus, and syphilis
- Heavy metal tests – to detect toxin exposure
- Tests for medications such as phenytoin, long-term use of which can cause peripheral neuropathy
- Complete blood count (CBC) – to detect blood cell abnormalities, infection, and metabolic problems
- Serum protein electrophoresis (SPEP) – to rule out monoclonal gammopathy and, if indicated, followed by immunofixation electrophoresis (IFE) or an equivalent test (e.g., capillary zone electrophoresis-based immunotyping)
- Paraneoplastic antibodies, if recommended by a specialist (e.g., neurologist)
- Rarely, genetic testing to identify certain inherited disorders
Some labs offer a panel of antibody tests, such as a motor neuropathy antibody panel and a sensory neuropathy antibody panel, to aid in diagnosis. Elevations in certain antibodies have been associated with various neuropathies.
The goals of neuropathy treatment are to manage the underlying cause of the condition and relieve symptoms. Nerves can regenerate in some cases, and symptoms may resolve or improve over time when neuropathy is caused by a condition that can be treated, such as a vitamin B deficiency.
Treatment will depend on and is directed against any known cause of the neuropathy. Symptom management may involve:
- Gaining control of underlying conditions, such as maintaining good blood glucose control in patients with diabetes and reducing the inflammation associated with autoimmune disorders
- Limiting smoking and alcohol consumption
- Eating a balanced diet and maintaining a healthy body weight
- Stretching and being physically active; limiting periods of immobility, which can increase pressure on nerves
- Avoiding exposure to toxins
- Protecting body parts that have diminished ability to feel pain, heat, cold, and vibration from injury
- Supporting affected body parts with, for example, braces or orthopedic shoes
- Monitoring affected areas frequently and promptly addressing problems such as reddened skin and sores that may worsen and become infected
Several classes of medications are used to help alleviate neuropathic pain. They range from over-the-counter analgesics for mild pain to anti-seizure medications, antidepressants, and narcotic drugs for more severe pain. Surgical procedures may be necessary in some cases to release trapped or compressed nerves.
Complimentary therapies, such as physical therapy, acupuncture, massage, and transcutaneous electrical nerve stimulation (TENS), may also help bring pain relief.
People should work with their healthcare providers to determine the best treatments for their condition. A person’s needs often change over time, and new and alternative treatments continue to be developed.
Sources Used in Current Review
National Institute of Neurological Disorders and Stroke (December 2014). Peripheral Neuropathy Fact Sheet. Available online at http://www.ninds.nih.gov/disorders/peripheralneuropathy/detail_peripheralneuropathy.htm. Accessed May 19, 2016.
The Foundation for Peripheral Neuropathy. Available online at https://www.foundationforpn.org. Accessed May 19, 2016.
Mayo Clinic (20 May 2016 updated). Peripheral Neuropathy. Available online at http://www.mayoclinic.org/diseases-conditions/peripheral-neuropathy/home/ovc-20204944. Accessed May 20, 2016.
Azhary H, Farooq MU, Bhanushali M, et al. Peripheral Neuropathy: Differential Diagnosis and Management. American Family Physician. 2010;81 (7):887-892.
Quest Diagnostics. Laboratory Diagnosis of Peripheral Neuropathy. Available online at http://www.questdiagnostics.com/testcenter/testguide.action?dc=WP_LabDiagnosis_PeripheralNeurop. Accessed November 2016.
Mikhael, Joseph. A Diagnostic Approach to Patients with an IgM Monoclonal Protein. The Hematologist. September-October 2014, Volume 11, Issue 5. Available online at http://www.hematology.org/Thehematologist/Ask/3186.aspx. Accessed November 2016.
Ramchandren S1, Lewis RA. An update on monoclonal gammopathy and neuropathy. Curr Neurol Neurosci Rep. 2012 Feb;12(1):102-10. Available online at https://www.ncbi.nlm.nih.gov/pubmed/22090258. Accessed November 2016.
Sources Used in Previous Reviews
Dugdale, D. (Updated 2010 August 27). Peripheral neuropathy. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000593.htm. Accessed May 2011.
(2010 April 21). Peripheral Neuropathy. JAMA Patient Page v 303 (15) [On-line information]. PDF available for download at http://jama.ama-assn.org/content/303/15/1556.full.pdf. Accessed May 2011.
(Updated 2011 February 18) Peripheral Neuropathy Fact Sheet. National Institute of Neurological Disorders and Stroke [On-line information]. Available online at http://www.ninds.nih.gov/disorders/peripheralneuropathy/detail_peripheralneuropathy.htm. Accessed May 2011.
Lin, H. (Updated 2011 May 13). Diabetic Neuropathy. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/1170337-overview. Accessed May 2011.
Sewell, A. (Updated 2010 September 27). Nutritional Neuropathy. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/1171558-overview. Accessed May 2011.
Hill, H and Tebo, A. (Updated 2011 April). Neuropathic Disease. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/NeuropathicDz.html?client_ID=LTD. Accessed May 2011.
(2009 February). Diabetic Neuropathies: The Nerve Damage of Diabetes National Diabetes Information Clearinghouse [On-line information]. Available online at http://diabetes.niddk.nih.gov/dm/pubs/neuropathies/. Accessed May 2011.
Mayo Clinic Staff (2009 November 3). Peripheral Neuropathy. MayoClinic.com [On-line information]. Available online at http://www.mayoclinic.com/health/peripheral-neuropathy/DS00131/METHOD=print. Accessed May 2011.
Mayo Clinic Staff (2010 April 15). Autonomic Neuropathy. MayoClinic.com [On-line information]. Available online at http://www.mayoclinic.com/health/autonomic-neuropathy/DS00544/METHOD=print. Accessed May 2011.
(Updated 2011 March 22). Giant Axonal Neuropathy. National Institute of Neurological Disorders and Stroke [On-line information]. Available online at http://www.ninds.nih.gov/disorders/gan/GiantAxonalNeuropathy.htm. Accessed May 2011.
(Updated 2011 February 15). Charcot-Marie-Tooth Disease Fact Sheet. National Institute of Neurological Disorders and Stroke [On-line information]. Available online at http://www.ninds.nih.gov/disorders/charcot_marie_tooth/detail_charcot_marie_tooth.htm. Accessed May 2011.
Dugdale, D. (Updated 2010 August 27). Alcoholic neuropathy. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000714.htm. Accessed May 2011.
Eckman, A. (Updated 2010 April 19). Diabetic neuropathy. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000693.htm. Accessed May 2011.
Rubin, M. (Revised 2008 February). Peripheral Neuropathy. Merck Manual for Healthcare Professionals [On-line information]. Available online at http://www.merckmanuals.com/professional/sec16/ch223/ch223h.html?qt=neuropathy&alt=sh. Accessed May 2011. [On-line information]. Available online at
Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL eds, (2005) Harrison’s Principles of Internal Medicine, 16th Edition, McGraw Hill, Pp 2500-2509, 2510-2514.
What is Neuropathy? Neuropathy Causes and Treatments. Medical News Today. Article date 29 Apr 2009. Available online at http://www.medicalnewstoday.com/articles/147963.php. Accessed August 2011.
ARUP Lab Tests. Motor Neuropathy Panel. Available online at http://www.aruplab.com/guides/ug/tests/0051225.jsp. Accessed August 2011.
Mayo Clinic. 57234 Clinical: Motor Neuropathy Antibody Panel (Serum). Available online at http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/57234. Accessed August 2011.
ARUP Lab Tests. Sensory Neuropathy Antibody Panel with Reflex to PCCA Titer, ANNA Titer & Neuronal Immunoblot. Available online at http://www.aruplab.com/guides/ug/tests/0051222.jsp. Accessed August 2011.
Quest Diagnostics. Motor and Sensory Neuropathy Panel. Available online at http://www.questdiagnostics.com/hcp/testmenu/jsp/showTestMenu.jsp?s=M&test_code=95775&fn=17540X.html&labCode=SJC. Accessed August 2011.
Nervous System Information. Body Guide, Powered by ADAM. Available online at http://www.pennmedicine.org/health_info/body_guide/reftext/html/nerv_sys_fin.html. Accessed August 2011.
Neuropathic Pain. Weill Cornell Pain Medical College. Available online at http://www.cornellpainmedicine.com/health_library/neuropathic_pain.html. Accessed August 2011.
Dr. Wayne Moore, Neuropathologist. Vancouver General Hospital Associate Professor, Dept. of Pathology & Laboratory Medicine, The University of British Columbia Vancouver, Canada.