|Classification and external resources|
|Patient UK||Peripheral neuropathy|
Peripheral neuropathy (PN) is damage or disease affecting nerves, which may impair sensation, movement, gland or organ function, or other aspects of health, depending on the type of nerve affected. Common causes include systemic diseases (such as diabetes or leprosy), vitamin deficiency, medication (e.g., chemotherapy), traumatic injury, excessive alcohol consumption, immune system disease, or infection, or it may be inherited (present from birth). In conventional medical usage, the word neuropathy (neuro-, "nervous system" and -pathy, "disease of") without modifier usually means peripheral neuropathy.
Neuropathy affecting just one nerve is called "mononeuropathy" and neuropathy involving multiple nerves in roughly the same areas on both sides of the body is called "symmetrical polyneuropathy" or simply "polyneuropathy." When two or more (typically just a few, but sometimes many) separate nerves in disparate areas of the body are affected it is called "mononeuritis multiplex," "multifocal mononeuropathy" or "multiple mononeuropathy."
Peripheral neuropathy may be chronic (a long term condition where symptoms begin subtly and progress slowly) or acute (sudden onset, rapid progress and slow resolution). Acute neuropathies demand urgent diagnosis. Motor nerves (that control muscles), sensory nerves, or autonomic nerves (that control automatic functions such as heart rate, body temperature and breathing), may be affected. More than one type of nerve may be affected at the same time. Peripheral neuropathies may be classified according to the type of nerve predominantly involved, or by the underlying cause. Where the cause is unknown it is described as idiopathic neuropathy.
Neuropathy may cause painful cramps, fasciculations (fine muscle twitching), muscle loss, bone degeneration, and changes in the skin, hair, and nails. Additionally, motor neuropathy may cause impaired balance and coordination or, most commonly, muscle weakness; sensory neuropathy may cause numbness to touch and vibration, reduced position sense causing poorer coordination and balance, reduced sensitivity to temperature change and pain, spontaneous tingling or burning pain, or skin allodynia (severe pain from normally nonpainful stimuli, such as light touch); and autonomic neuropathy may produce diverse symptoms, depending on the affected glands and organs, but common symptoms are poor bladder control, abnormal blood pressure or heart rate, and reduced ability to sweat normally.
Peripheral neuropathy may be classified according to the number and distribution of nerves affected (mononeuropathy, mononeuritis multiplex or polyneuropathy), the type of nerve cell predominantly affected (motor, sensory, autonomic), or the process affecting the nerves; e.g., inflammation (neuritis), compression (compression neuropathy), chemotherapy (chemotherapy-induced peripheral neuropathy).
Mononeuropathy is a type of neuropathy that only affects a single nerve. It is diagnostically useful to distinguish it from polyneuropathy because the limitation in scope makes it more likely that the cause is a localized trauma or infection.
The most common cause of mononeuropathy is physical compression of the nerve, known as compression neuropathy. Carpal tunnel syndrome and axillary nerve palsy are examples of this. The "pins-and-needles" sensation of one's "foot falling asleep" (paresthesia) is caused by a compression mononeuropathy, albeit a temporary one which can be resolved merely by moving around and adjusting to a more appropriate position. Direct injury to a nerve, interruption of its blood supply (ischemia), or inflammation can also cause mononeuropathy.
Mononeuritis multiplex, occasionally termed polyneuritis multiplex, is simultaneous or sequential involvement of individual noncontiguous nerve trunks, either partially or completely, evolving over days to years and typically presenting with acute or subacute loss of sensory and motor function of individual nerves. The pattern of involvement is asymmetric; however, as the disease progresses deficit(s) becomes more confluent and symmetrical, making it difficult to differentiate from polyneuropathy. Therefore, attention to the pattern of early symptoms is important.
Mononeuritis multiplex may also cause pain, which is characterized as deep, aching pain that is worse at night and frequently in the lower back, hip, or leg. In people with diabetes mellitus, mononeuritis multiplex is typically encountered as acute, unilateral, severe thigh pain followed by anterior muscle weakness and loss of knee reflex.
Electrodiagnostic studies will show multifocal sensory motor axonal neuropathy.
It is caused by, or associated with, several medical conditions:
- diabetes mellitus
- vasculitides: polyarteritis nodosa, Wegener's granulomatosis, and Churg–Strauss syndrome
- immune-mediated diseases like rheumatoid arthritis, lupus erythematosus (SLE)
- infections: leprosy, lyme disease, HIV
- sarcoidosis, amyloidosis
- chemical agents, including trichloroethylene and dapsone
- rarely, the sting of certain jellyfish, such as the sea nettle
Polyneuropathy is a pattern of nerve damage which is quite different from mononeuropathy, often more serious and affecting more areas of the body. The term "peripheral neuropathy" is sometimes used loosely to refer to polyneuropathy. In cases of polyneuropathy, many nerve cells in various parts of the body are affected, without regard to the nerve through which they pass; not all nerve cells are affected in any particular case. In distal axonopathy, one common pattern is that the cell bodies of neurons remain intact, but the axons are affected in proportion to their length. Diabetic neuropathy is the most common cause of this pattern. In demyelinating polyneuropathies, the myelin sheath around axons is damaged, which affects the ability of the axons to conduct electrical impulses. The third and least common pattern affects the cell bodies of neurones directly. This usually picks out either the motor neurones (known as motor neurone disease) or the sensory neurones (known as sensory neuronopathy or dorsal root ganglionopathy).
The effect of this is to cause symptoms in more than one part of the body, often on left and right sides symmetrically. As for any neuropathy, the chief symptoms include weakness or clumsiness of movement (motor); unusual or unpleasant sensations such as tingling or burning; reduction in the ability to feel texture, temperature, etc.; and impaired balance when standing or walking (sensory). In many polyneuropathies, these symptoms occur first and most severely in the feet. Autonomic symptoms may also occur, such as dizziness on standing up, erectile dysfunction, and difficulty controlling urination.
Polyneuropathies are usually caused by processes that affect the body as a whole. Diabetes and impaired glucose tolerance are the most common causes. Other causes relate to the particular type of polyneuropathy, and there are many different causes of each type, including inflammatory diseases such as lyme disease, vitamin deficiencies, blood disorders, and toxins (including alcohol and certain prescribed drugs). Most types of polyneuropathy progress fairly slowly, over months or years, but rapidly progressive polyneuropathy also occurs. It is important to recognize that glucose levels in the blood can spike to nerve-damaging levels after eating even though fasting blood sugar levels and average blood glucose levels can still remain below normal levels (currently typically considered below 100 mg/dL for fasting blood plasma and 6.0% for HGBA1c, the test commonly used to measure average blood glucose levels over an extended period). Studies have shown that many of the cases of peripheral small fiber neuropathy with typical symptoms of tingling, pain, and loss of sensation in the feet and hands are due to glucose intolerance before a diagnosis of diabetes or pre-diabetes. Such damage is often reversible, particularly in the early stages, with diet, exercise, and weight loss.
The treatment of polyneuropathies is aimed firstly at eliminating or controlling the cause, secondly at maintaining muscle strength and physical function, and thirdly at controlling symptoms such as neuropathic pain.
Autonomic neuropathy is a form of polyneuropathy which affects the non-voluntary, non-sensory nervous system (i.e., the autonomic nervous system), affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Autonomic nerve fibers form large collections in the thorax, abdomen, and pelvis outside the spinal cord. However, they have connections with the spinal cord and ultimately the brain. Most commonly autonomic neuropathy is seen in persons with long-standing diabetes mellitus type 1 and 2. In most but not all cases, autonomic neuropathy occurs alongside other forms of neuropathy, such as sensory neuropathy.
Autonomic neuropathy is one cause of malfunction of the autonomic nervous system but not the only one; some conditions affecting the brain or spinal cord can also cause autonomic dysfunction, such as multiple system atrophy, and therefore cause similar symptoms to autonomic neuropathy.
The signs and symptoms of autonomic neuropathy include the following:
- Urinary bladder conditions: bladder incontinence or urine retention
- Gastrointestinal tract: dysphagia, abdominal pain, nausea, vomiting, malabsorption, fecal incontinence, gastroparesis, diarrhoea, constipation
- Cardiovascular system: disturbances of heart rate (tachycardia, bradycardia), orthostatic hypotension, inadequate increase of heart rate on exertion
- Respiratory system: impairments in the signals associated with regulation of breathing and gas exchange (central sleep apnea, hypopnea, bradypnea).
- Other areas: hypoglycemia unawareness, genital impotence, sweat disturbances
Neuritis is a general term for inflammation of a nerve or the general inflammation of the peripheral nervous system. Symptoms depend on the nerves involved but may include pain, paresthesia (pins & needles), paresis (weakness), hypoesthesia (numbness), anesthesia, paralysis, wasting, and disappearance of the reflexes. Causes include:
- One common cause of neuritis and subsequent inflammation of the nerves to the toes is the wearing of high-heeled shoes or ill-fitting shoes that bind the toes painfully. This can cause temporary numbness and pain in the affected toes for several days.
- Chemical injury
- Underlying conditions causing localized neuritis (affecting a single nerve):
- Underlying conditions causing polyneuritis (affecting multiple nerves):
- Beriberi (vitamin B1 deficiency)
- Vitamin B12 deficiency
- Vitamin B6 excess
- Metabolic diseases
- Celiac disease
- Herpes zoster
- Infections, bacterial and/or viral
- Autoimmune disease, especially multiple sclerosis and Guillain-Barre syndrome
- Wartenberg's migratory sensory neuropathy
Types of neuritis include:
- Polyneuritis or multiple neuritis (not to be confused with multiple sclerosis)
- Brachial neuritis
- Optic neuritis
- Vestibular neuritis
- Cranial neuritis, often representing as Bell's palsy
- Arsenic neuritis
Signs and symptoms
|This section does not cite any references or sources. (January 2013)|
Those with diseases or dysfunctions of their nerves can present with problems in any of the normal nerve functions.
Gain of function (positive) symptoms include tingling, pain, itching, crawling, and pins and needles. Pain can become intense enough to require use of opioid (narcotic) drugs (i.e., morphine, oxycodone).
Motor symptoms include loss of function (negative) symptoms of weakness, tiredness, heaviness, and gait abnormalities; and gain of function (positive) symptoms of cramps, tremor, and muscle twitch (fasciculations).
During physical examination, specifically a neurological examination, those with generalized peripheral neuropathies most commonly have distal sensory or motor and sensory loss, though those with a pathology (problem) of the nerves may be perfectly normal; may show proximal weakness, as in some inflammatory neuropathies like Guillain–Barré syndrome; or may show focal sensory disturbance or weakness, such as in mononeuropathies. Ankle jerk reflex is classically absent in peripheral neuropathy.
The causes are broadly grouped as follows:
- Genetic diseases: Friedreich's ataxia, Charcot-Marie-Tooth disease, hereditary neuropathy with liability to pressure palsy
- Metabolic/endocrine: diabetes mellitus, chronic renal failure, porphyria, amyloidosis, liver failure, hypothyroidism
- Toxic causes: drugs (vincristine, metronidazole, phenytoin, nitrofurantoin, isoniazid, ethyl alcohol, statins), organic herbicides TCDD dioxin, organic metals, heavy metals, excess intake of vitamin B6 (pyridoxine). Peripheral neuropathies can also result from long term (more than 21 days) treatment with Linezolid (Zyvox).
- Adverse effects of fluoroquinolones: Irreversible neuropathy is a serious adverse reaction of fluoroquinolone drugs
- Inflammatory diseases: Guillain-Barré syndrome, systemic lupus erythematosus, leprosy, multiple sclerosis, Sjögren's syndrome, Lyme disease, sarcoidosis,
- Vitamin deficiency states: Vitamin B12 (Methylcobalamin), vitamin A, vitamin E, vitamin B1 (thiamin)
- Physical trauma: compression, pinching, cutting, projectile injuries (for example, gunshot wound), strokes including prolonged occlusion of blood flow, electric discharge, including lightning strikes
- Chemotherapy - see Chemotherapy-induced peripheral neuropathy
- Others: electric shock, HIV, malignant disease, radiation, shingles
Many treatment strategies for peripheral neuropathy are symptomatic. Some current research in animal models has shown that neurotrophin-3 can oppose the demyelination present in some peripheral neuropathies.
A range of drugs that act on the central nervous system such as drugs originally intended as antidepressants and antiepileptic drugs have been found to be useful in managing neuropathic pain. Commonly used treatments include using a tricyclic antidepressant (such as amitriptyline) and antiepileptic therapies such as gabapentin or sodium valproate. These have the advantage that besides being effective in many cases they are relatively low cost.
A great deal of research has been done between 2005 and 2010 which indicates that synthetic cannabinoids and inhaled cannabis are effective treatments for a range of neuropathic disorders. Research has demonstrated that the synthetic oral cannabinoid Nabilone is an effective adjunct treatment option for neuropathic conditions, especially for people who are resistant, intolerant, or allergic to common medications. Orally, opiate derivatives were found to be more effective than cannabis for most people. Smoked cannabis has been found to provide relief from HIV-associated sensory neuropathy. Smoked cannabis was also found to relieve neuropathy associated with CRPS type I, spinal cord injury, peripheral neuropathy, and nerve injury.
Pregabalin is an anticonvulsant drug used for neuropathic pain. It has also been found effective for generalized anxiety disorder. It was designed as a more potent successor to gabapentin but is significantly more expensive, especially now that the patent on gabapentin has expired and gabapentin is available as a generic drug. Pregabalin is marketed by Pfizer under the trade name Lyrica.
Transcutaneous electrical nerve stimulation therapy may be effective and safe in the treatment of diabetic peripheral neuropathy. A recent review of three trials involving 78 patients found some improvement in pain scores after 4 and 6 but not 12 weeks of treatment, and an overall improvement in neuropathic symptoms at 12 weeks. A second review of four trials found significant improvement in pain and overall symptoms, with 38% of patients in one trial becoming asymptomatic. The treatment remains effective even after prolonged use, but symptoms return to baseline within a month of treatment cessation.
Neuropathy has been reported to make winter weather more perilous for older adults. Often, people with neuropathy who live in areas with defined winters (such as the northern United States) report that their symptoms were much less severe after moving to places with an undefined winter, such as Florida or California.
Symptomatic relief for the pain of peripheral neuropathy is sometimes obtained by application of topical capsacin. Capsacin is the factor which causes heat in chili peppers. Relief up to 12 weeks is noted with high concentrations of capsacin applied cutaneously. Local anesthesia is often used to counteract the initial discomfort of the capsacin. More information is available in this review by the National Institue of Health. 
- Richard A C Hughes (23 February 2002). "Clinical review: Peripheral neuropathy". British Medical Journal 324: 466. doi:10.1136/bmj.324.7335.466.
- Janet M. Torpy; Jennifer L. Kincaid; Richard M. Glass (21 April 2010). "Patient page: Peripheral neuropathy". Journal of the American Medical Association 303 (15). doi:10.1001/jama.303.15.1556.
- "Peripheral neuropathy fact sheet". National Institute of Neurological Disorders and Stroke. 19 September 2012.
- "neuropathy". Online Etymology Dictionary.
- "Dorlands Medical Dictionary:mononeuropathy".
- Vinik, AI; Erbas, T (2013). "Diabetic autonomic neuropathy.". Handbook of clinical neurology 117: 279–94. doi:10.1016/b978-0-444-53491-0.00022-5. PMID 24095132.
- "neuritis" at Dorland's Medical Dictionary
- Rosenbloom, Mark; Tarabar, Asim; Adler, Robert A. "Vitamin Toxicity". Medscape Reference. Medscape. Retrieved 21 May 2013.
- Chin, RL; Latov, N (Jan 2005). "Peripheral Neuropathy and Celiac Disease.". Current treatment options in neurology 7 (1): 43–48. doi:10.1007/s11940-005-0005-3. PMID 15610706.
- Gabriel JM, Erne B, Pareyson D, Sghirlanzoni A, Taroni F, Steck AJ (1997). "Gene dosage effects in hereditary peripheral neuropathy. Expression of peripheral myelin protein 22 in Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies nerve biopsies". Neurology 49 (6): 1635–40. doi:10.1212/WNL.49.6.1635. PMID 9409359.
- Kiziltan ME, Akalin MA, Sahin R, Uluduz D (2007). "Peripheral neuropathy in patients with diabetes mellitus presenting as Bell's palsy". Neuroscience Letters 427 (3): 138–41. doi:10.1016/j.neulet.2007.09.029. PMID 17933462.
- "Statin Drugs May Increase Risk Of Peripheral Neuropathy". ScienceDaily (St. Paul, Minnesota). 15 May 2002. Retrieved 21 May 2013.
- "Statin Drugs May Increase Risk of Peripheral Neuropathy". AAN.com (Press release). St. Paul, Minnesota: American Academy of Neurology. 13 May 2002. Retrieved 21 May 2013.
- Cohen, JS (December 2001). "Peripheral Neuropathy Associated with Fluoroquinolones" (PDF). Ann Pharmacother 35 (12): 1540–7. doi:10.1345/aph.1Z429. PMID 11793615.
- Heck AW, Phillips LH 2nd (1989). "Sarcoidosis and the nervous system". Neurol Clin 7 (3): 641–54. PMID 2671639.
- Wilkes, G (2007). "Peripheral neuropathy related to chemotherapy". Seminars in oncology nursing 23 (3): 162–73. doi:10.1016/j.soncn.2007.05.001. PMID 17693343.
- Gonzalez-Duarte, A; Cikurel, K; Simpson, DM (2007). "Managing HIV peripheral neuropathy". Current HIV/AIDS reports 4 (3): 114–8. doi:10.1007/s11904-007-0017-6. PMID 17883996.
- Liu N, Varma S, Tsao D, Shooter EM, Tolwani RJ (2007). "Depleting endogenous neurotrophin-3 enhances myelin formation in the Trembler-J mouse, a model of a peripheral neuropathy". J. Neurosci. Res. 85 (13): 2863–9. doi:10.1002/jnr.21388. PMID 17628499.
- Hazekamp, Arno; Grotenhermen, Franjo (2010). "Review on clinical studies with cannabis and cannabinoids 2005-2009". Cannabinoids (International Association for Cannabinoid Medicines) (5): 1–21. Retrieved 21 May 2013.
- Skrabek RQ, Galimova L, Ethans K, Perry D (2008). "Nabilone for the treatment of pain in fibromyalgia". J. Pain 9 (2): 164–73. doi:10.1016/j.jpain.2007.09.002. PMID 17974490.
- Frank B, Serpell MG, Hughes J, Matthews JN, Kapur D (2008). "Comparison of analgesic effects and patient toleration of nabilone and dihydrocodeine for chronic neuropathic pain: randomized, crossover, double blind study". BMJ 336 (7637): 119–201. doi:10.1136/bmj.39429.619653.80. PMC 2213874. PMID 18182416.
- Abrams DI, Jay CA, Shade SB, Vizozo H, Reda H, Press S, Kelly ME, Rowbotham Mc, Petersen KL (2007). "Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trail". J. Neurology 68 (7): 515–21. doi:10.1212/01.wnl.0000253187.66183.9c. PMID 17296917.
- Wilsey B, Marcotte T, Tsodikov A, Millman J, Bentley H, Gouaux B, Fishman S (2008). "A randomized, placebo-controlled, crossover trail of cannabis cigarettes in neuropathic pain". J. Pain 9 (6): 506–21. doi:10.1016/j.jpain.2007.12.010. PMID 18403272.
- Jin DM, Xu Y, Geng DF, Yan TB (July 2010). "Effect of transcutaneous electrical nerve stimulation on symptomatic diabetic peripheral neuropathy: a meta-analysis of randomized controlled trials". Diabetes Res. Clin. Pract. 89 (1): 10–5. doi:10.1016/j.diabres.2010.03.021. PMID 20510476.
- Pieber K, Herceg M, Paternostro-Sluga T (April 2010). "Electrotherapy for the treatment of painful diabetic peripheral neuropathy: a review". J Rehabil Med 42 (4): 289–95. doi:10.2340/16501977-0554. PMID 20461329.
- Dillon, Helen (21 December 2009). "Neuropathy can make winter weather more perilous for older adults". All Things Aging. Retrieved 10 March 2012.
- Latov, Norman (2007). Peripheral Neuropathy: When the Numbness, Weakness, and Pain Won't Stop. New York: American Academy of Neurology Press Demos Medical. ISBN 1-932603-59-X.
- Committee on Standards and Practice Parameters, American Society of Anesthesiologists (2011). "Practice advisory for the prevention of perioperative peripheral neuropathies: an updated report by the American Society of Anesthesiologists Task Force on prevention of perioperative peripheral neuropathies". Anesthesiology 114 (4): 1168–82. PMID 10754638.