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| {{Infobox_Disease |
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| Name = {{PAGENAME}} |
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| Image = |
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| Caption = |
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| DiseasesDB = 9850 |
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| ICD10 = {{ICD10|G|64||g|60}}, {{ICD10|G|90|0|g|90}} |
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| ICD9 = {{ICD9|356}} |
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| ICDO = |
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| OMIM = |
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| MedlinePlus = |
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| eMedicineSubj = |
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| eMedicineTopic = |
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| MeshID = D010523 |
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| }}
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| {{Search infobox}}
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| {{CMG}}
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| __NOTOC__ | | __NOTOC__ |
| {{Editor Help}} | | {{Peripheral neuropathy}} |
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| ==Overview==
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| Peripheral neuropathy describes damage to the peripheral nervous system, the vast communications network that transmits information from the brain and spinal cord (the central nervous system) to every other part of the body. Peripheral nerves also send sensory information back to the brain and spinal cord, such as a message that the feet are cold or a finger is burned. Damage to the peripheral nervous system interferes with these vital connections. Like static on a telephone line, peripheral neuropathy distorts and sometimes interrupts messages between the brain and the rest of the body. | | {{CMG}} {{AE}} {{MMJ}} |
| Because every peripheral nerve has a highly specialized function in a specific part of the body, a wide array of symptoms can occur when nerves are damaged. Some people may experience temporary numbness, tingling, and pricking sensations (paresthesia), sensitivity to touch, or muscle weakness. Others may suffer more extreme symptoms, including burning pain (especially at night), muscle wasting, paralysis, or organ or gland dysfunction. People may become unable to digest food easily, maintain safe levels of blood pressure, sweat normally, or experience normal sexual function. In the most extreme cases, breathing may become difficult or organ failure may occur.
| | ==[[Peripheral neuropathy overview|Overview]]== |
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| Some forms of neuropathy involve damage to only one nerve and are called mononeuropathies. More often though, multiple nerves affecting all limbs are affected-called polyneuropathy. Occasionally, two or more isolated nerves in separate areas of the body are affected-called mononeuritis multiplex.
| | ==[[Peripheral neuropathy classification|Classification]]== |
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| In acute neuropathies, such as Guillain-Barré syndrome, symptoms appear suddenly, progress rapidly, and resolve slowly as damaged nerves heal. In chronic forms, symptoms begin subtly and progress slowly. Some people may have periods of relief followed by relapse. Others may reach a plateau stage where symptoms stay the same for many months or years. Some chronic neuropathies worsen over time, but very few forms prove fatal unless complicated by other diseases. Occasionally the neuropathy is a symptom of another disorder.
| | ==[[Peripheral neuropathy pathophysiology|Pathophysiology]]== |
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| In the most common forms of polyneuropathy, the nerve fibers (individual cells that make up the nerve) most distant from the brain and the spinal cord malfunction first. Pain and other symptoms often appear symmetrically, for example, in both feet followed by a gradual progression up both legs. Next, the fingers, hands, and arms may become affected, and symptoms can progress into the central part of the body. Many people with diabetic neuropathy experience this pattern of ascending nerve damage.
| | ==[[Peripheral neuropathy causes|Causes]]== |
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| ==Types== | | ==[[Peripheral neuropathy differential diagnosis|Differentiating Peripheral Neuropathy from other Diseases]]== |
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| More than 100 types of peripheral neuropathy have been identified, each with its own characteristic set of symptoms, pattern of development, and prognosis. Impaired function and symptoms depend on the type of nerves-motor, sensory, or autonomic-that are damaged. Motor nerves control movements of all muscles under conscious control, such as those used for walking, grasping things, or talking. Sensory nerves transmit information about sensory experiences, such as the feeling of a light touch or the pain resulting from a cut. Autonomic nerves regulate biological activities that people do not control consciously, such as breathing, digesting food, and heart and gland functions. Although some neuropathies may affect all three types of nerves, others primarily affect one or two types. Therefore, physicians may use terms such as predominantly motor neuropathy, predominantly sensory neuropathy, sensory-motor neuropathy, or autonomic neuropathy to describe a patient's condition.
| | ==[[Peripheral neuropathy epidemiology and demographics|Epidemiology and Demographics]]== |
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| Often the form of neuropathy is further broken down as to cause (see below), or other type, such as [[small fiber peripheral neuropathy]], which is [[idiopathic]].
| | ==[[Peripheral neuropathy risk factors|Risk Factors]]== |
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| There are other less common forms of neuropathy, for example [[Enteric Neuropathy]]
| | ==[[Peripheral neuropathy natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| Peripheral neuropathy is not a disease in itself, but a symptom or a complication of other underlying conditions. Peripheral nerves, either singly or in groups, are damaged through lack of circulation, chemical imbalance, trauma, or other factors.<ref>Ruth Werner, LMP, NCTMB A Massage Therapist's Guide to Pathology; Third Edition Copyright 2005</ref>
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| Peripheral neuropathies may either be ''symmetrical'' and ''generalized'' or ''focal'' and ''multifocal'', which is usually a good indicator of the cause of the peripheral nerve disease.
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| === Generalized peripheral neuropathy === | |
| Generalized peripheral neuropathies are symmetrical, and usually due to various systematic illnesses and disease processes that affect the [[peripheral nervous system]] in its entirety.
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| They are further subdivided into several categories:
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| * '''[[Distal axonopathy|Distal axonopathies]]''' are the result of some metabolic or toxic derangement of [[neuron]]s. They may be caused by metabolic diseases such as [[diabetes]], [[renal failure]], deficiency syndromes such as [[malnutrition]] and [[alcoholism]], or the effects of [[toxin]]s or [[medication|drugs]].
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| * '''[[Myelinopathy|Myelinopathies]]''' are due to a primary attack on [[myelin]] causing an acute failure of impulse conduction. The most common cause is [[acute inflammatory demyelinating polyneuropathy]] (AIDP; ''aka'' [[Guillain-Barré syndrome]]), though other causes include [[chronic inflammatory demyelinating polyneuropathy]] (CIDP), [[genetics|genetic]] metabolic disorders (''e.g.'', [[leukodystrophy]]), or toxins.
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| * '''[[Neuronopathy|Neuronopathies]]''' are the result of destruction of [[peripheral nervous system]] (PNS) [[neuron]]s. They may be caused by [[motor neurone disease]]s, sensory neuronopathies (''e.g.'', [[Herpes zoster]]), toxins or [[autonomic nervous system|autonomic]] dysfunction. [[Neurotoxicity|Neurotoxins]] may cause neuronopathies, such as the [[chemotherapy]] agent [[vincristine]].
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| ==Causes==
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| '''Peripheral neuropathy''' may be either inherited or acquired. Causes of acquired peripheral neuropathy include physical injury (trauma) to a nerve, tumors, toxins, autoimmune responses, nutritional deficiencies, alcoholism, and vascular and metabolic disorders. Acquired peripheral neuropathies are grouped into three broad categories: those caused by systemic disease, those caused by trauma from external agents, and those caused by infections or autoimmune disorders affecting nerve tissue. One example of an acquired peripheral neuropathy is trigeminal neuralgia (also known as tic douloureux), in which damage to the trigeminal nerve (the large nerve of the head and face) causes episodic attacks of excruciating, lightning-like pain on one side of the face. In some cases, the cause is an earlier viral infection, pressure on the nerve from a tumor or swollen blood vessel, or, infrequently, multiple sclerosis. In many cases, however, a specific cause cannot be identified. Doctors usually refer to neuropathies with no known cause as idiopathic neuropathies.
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| '''Physical injury''' (trauma) is the most common cause of injury to a nerve. Injury or sudden trauma, such as from automobile accidents, falls, and sports-related activities, can cause nerves to be partially or completely severed, crushed, compressed, or stretched, sometimes so forcefully that they are partially or completely detached from the spinal cord. Less dramatic traumas also can cause serious nerve damage. Broken or dislocated bones can exert damaging pressure on neighboring nerves, and slipped disks between vertebrae can compress nerve fibers where they emerge from the spinal cord.
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| '''Systemic diseases:''' disorders that affect the entire body —often cause peripheral neuropathy. These disorders may include: Metabolic and endocrine disorders. Nerve tissues are highly vulnerable to damage from diseases that impair the body's ability to transform nutrients into energy, process waste products, or manufacture the substances that make up living tissue. Diabetes mellitus, characterized by chronically high blood glucose levels, is a leading cause of peripheral neuropathy in the United States. About 60 percent to 70 percent of people with diabetes have mild to severe forms of nervous system damage.
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| '''Kidney disorders''' can lead to abnormally high amounts of toxic substances in the blood that can severely damage nerve tissue. A majority of patients who require dialysis because of kidney failure develop polyneuropathy. Some liver diseases also lead to neuropathies as a result of chemical imbalances.
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| '''Hormonal imbalances''' can disturb normal metabolic processes and cause neuropathies. For example, an underproduction of thyroid hormones slows metabolism, leading to fluid retention and swollen tissues that can exert pressure on peripheral nerves. Overproduction of growth hormone can lead to acromegaly, a condition characterized by the abnormal enlargement of many parts of the skeleton, including the joints. Nerves running through these affected joints often become entrapped.
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| '''Vitamin deficiencies''' and alcoholism can cause widespread damage to nerve tissue. Vitamins E, B1, B6, B12, and niacin are essential to healthy nerve function. Thiamine deficiency, in particular, is common among people with alcoholism because they often also have poor dietary habits. Thiamine deficiency can cause a painful neuropathy of the extremities. Some researchers believe that excessive alcohol consumption may, in itself, contribute directly to nerve damage, a condition referred to as alcoholic neuropathy.
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| '''Vascular damage and blood diseases''' can decrease oxygen supply to the peripheral nerves and quickly lead to serious damage to or death of nerve tissues, much as a sudden lack of oxygen to the brain can cause a stroke. Diabetes frequently leads to blood vessel constriction. Various forms of vasculitis (blood vessel inflammation) frequently cause vessel walls to harden, thicken, and develop scar tissue, decreasing their diameter and impeding blood flow. This category of nerve damage, in which isolated nerves in different areas are damaged, is called mononeuropathy multiplex or multifocal mononeuropathy.
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| '''Connective tissue disorders and chronic inflammation''' can cause direct and indirect nerve damage. When the multiple layers of protective tissue surrounding nerves become inflamed, the inflammation can spread directly into nerve fibers. Chronic inflammation also leads to the progressive destruction of connective tissue, making nerve fibers more vulnerable to compression injuries and infections. Joints can become inflamed and swollen and entrap nerves, causing pain.
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| '''Cancers and benign tumors''' can infiltrate or exert damaging pressure on nerve fibers. Tumors also can arise directly from nerve tissue cells. Widespread polyneuropathy is often associated with the neurofibromatoses, genetic diseases in which multiple benign tumors grow on nerve tissue. Neuromas, benign masses of overgrown nerve tissue that can develop after any penetrating injury that severs nerve fibers, generate very intense pain signals and sometimes engulf neighboring nerves, leading to further damage and even greater pain. Neuroma formation can be one element of a more widespread neuropathic pain condition called complex regional pain syndrome or reflex sympathetic dystrophy syndrome, which can be caused by traumatic injuries or surgical trauma. Paraneoplastic syndromes, a group of rare degenerative disorders that are triggered by a person's immune system response to a cancerous tumor, also can indirectly cause widespread nerve damage.
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| '''Repetitive stress''' frequently leads to entrapment neuropathies, a special category of compression injury. Cumulative damage can result from repetitive, forceful, awkward activities that require flexing of any group of joints for prolonged periods. The resulting irritation may cause ligaments, tendons, and muscles to become inflamed and swollen, constricting the narrow passageways through which some nerves pass. These injuries become more frequent during pregnancy, probably because weight gain and fluid retention also constrict nerve passageways.
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| '''Toxins''' can also cause peripheral nerve damage. People who are exposed to heavy metals (arsenic, lead, mercury, thallium), industrial drugs, or environmental toxins frequently develop neuropathy. Certain anticancer drugs, anticonvulsants, antiviral agents, and antibiotics have side effects that can include peripheral nerve damage, thus limiting their long-term use.
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| '''Infections and autoimmune disorders''' can cause peripheral neuropathy. Viruses and bacteria that can attack nerve tissues include herpes varicella-zoster (shingles), Epstein-Barr virus, cytomegalovirus, and herpes simplex-members of the large family of human herpes viruses. These viruses severely damage sensory nerves, causing attacks of sharp, lightning-like pain. Postherpetic neuralgia often occurs after an attack of shingles and can be particularly painful.
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| '''The human immunodeficiency virus''' (HIV), which causes AIDS, also causes extensive damage to the central and peripheral nervous systems. The virus can cause several different forms of neuropathy, each strongly associated with a specific stage of active immunodeficiency disease. A rapidly progressive, painful polyneuropathy affecting the feet and hands is often the first clinically apparent sign of HIV infection.
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| '''Lyme disease''', diphtheria, and leprosy are bacterial diseases characterized by extensive peripheral nerve damage. Diphtheria and leprosy are now rare in the United States, but Lyme disease is on the rise. It can cause a wide range of neuropathic disorders, including a rapidly developing, painful polyneuropathy, often within a few weeks after initial infection by a tick bite.
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| '''Viral and bacterial infections''' can also cause indirect nerve damage by provoking conditions referred to as autoimmune disorders, in which specialized cells and antibodies of the immune system attack the body's own tissues. These attacks typically cause destruction of the nerve's myelin sheath or axon (the long fiber that extends out from the main nerve cell body).
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| Some neuropathies are caused by inflammation resulting from immune system activities rather than from direct damage by infectious organisms. Inflammatory neuropathies can develop quickly or slowly, and chronic forms can exhibit a pattern of alternating remission and relapse. Acute inflammatory demyelinating neuropathy, better known as Guillain-Barré syndrome, can damage motor, sensory, and autonomic nerve fibers. Most people recover from this syndrome although severe cases can be life threatening. Chronic inflammatory demyelinating polyneuropathy (CIDP), generally less dangerous, usually damages sensory and motor nerves, leaving autonomic nerves intact. Multifocal motor neuropathy is a form of inflammatory neuropathy that affects motor nerves exclusively; it may be chronic or acute.
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| Inherited forms of peripheral neuropathy are caused by inborn mistakes in the genetic code or by new genetic mutations. Some genetic errors lead to mild neuropathies with symptoms that begin in early adulthood and result in little, if any, significant impairment. More severe hereditary neuropathies often appear in infancy or childhood.
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| The most common inherited neuropathies are a group of disorders collectively referred to as Charcot-Marie-Tooth disease. These neuropathies result from flaws in genes responsible for manufacturing neurons or the myelin sheath. Hallmarks of typical Charcot-Marie-Tooth disease include extreme weakening and wasting of muscles in the lower legs and feet, gait abnormalities, loss of tendon reflexes, and numbness in the lower limbs.
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| As a summary; aside from diabetes (see [[Diabetic neuropathy]]), the common causes of neuropathy are [[herpes zoster]] infection, HIV-AIDS, toxins, alcoholism, chronic trauma (such as repetitive motion disorders) or acute trauma (including surgery), various neurotoxins and [[autoimmune]] conditions such as [[celiac disease]], which can account for approximately 16% of small fiber neuropathy cases.<ref>
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| {{cite web
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| | last =
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| | first =
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| | authorlink =
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| | coauthors =
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| | title = Up to 16% of Patients with Small Fiber Neuropathy May Have Celiac Disease
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| | work =
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| | publisher = Celiac.com
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| | date =
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| | url = http://www.celiac.com/st_prod.html?p_prodid=842
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| | format =
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| | doi =
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| | accessdate = 2007-26-06 }}
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| </ref> Neuropathic pain is common in [[cancer]] as a direct result of the cancer on peripheral nerves (e.g., compression by a tumor), as a side effect of many [[chemotherapy]] drugs, and as a result of [[electrical injury]]. In many cases the neuropathy is "idiopathic," meaning no cause is found. A form of spinal nerve entrapment called [[Posterior Rami Syndrome]] can led to neuropathic pain.
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| ===The List of Causes of {{PAGENAME}}===
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| *Genetic diseases:
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| :*[[Friedreich's ataxia]],
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| :*[[Charcot-Marie-Tooth syndrome]]
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| *Metabolic / Endocrine:
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| :*[[diabetes mellitus]],
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| :*[[Chronic renal failure]],
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| :*[[porphyria]],
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| :*[[amyloidosis]],
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| :*[[liver failure]],
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| :*[[hypothyroidism]]
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| *Toxic causes:
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| :*[[alcoholism]],
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| :*[[drug]]s
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| :*:*[[vincristine]],
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| :*:*[[phenytoin]],
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| :*:*[[isoniazid]],
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| :*organic metals,
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| :*:*[[heavy metals]]
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| *Inflammatory diseases:
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| :*[[Guillain-Barré syndrome]],
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| :*[[systemic lupus erythematosus]],
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| :*[[leprosy]],
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| :*[[Sjögren's syndrome]]
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| *Vitamin deficiency states:
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| :*[[vitamin B12|vitamin B<sub>12</sub>]],
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| :*[[vitamin A]],
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| :*[[vitamin E]],
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| :*[[thiamin]]
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| *Others:
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| *malignant disease,
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| *[[radiation]]
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| == Complete Differential Diagnosis for Peripheral Neuropathy ==
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| *[[Acromegaly]]
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| *[[Alcoholic polyneuropathy]]
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| *[[Atherosclerosis]]
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| *[[Amyloidosis]]
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| *[[Botulism]]
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| *[[Brucellosis]]
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| *[[Carpal Tunnel Syndrome]]
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| *[[Charcot-Marie-Tooth Disease]]
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| *Compression
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| *[[Diabetic polyneuropathy]]
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| *[[Diabetes Mellitus]]
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| *[[Diptheria]]
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| *[[Drugs]]
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| *[[Dysentery]]
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| *[[Dysproteinemia]]
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| *[[Fabry's Disease]]
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| *[[German Measles]]
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| *Hereditary [[Ataxia]]
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| *[[Herpes Zoster]]
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| *[[HIV]]
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| *[[Hypothyroidism]]
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| *[[Infectious Mononeucliosis]]
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| *[[Leukemia]]
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| *[[Lyme Disease]]
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| *[[Lymphoma]]
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| *[[Malaria]]
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| *[[Metachromatic leukodystrophy]]
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| *[[Multiple Myeloma]]
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| *[[Mycosis]]
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| *[[Paraneoplasia]]
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| *[[Paraproteinemia]]
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| *[[Paratyphus]]
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| *[[Pernicious anemia]]
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| *[[Polyarteritis Nodosa]]
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| *[[Polyrediculitis]]
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| *[[Porphyria]]
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| *Post-[[tetanus]] shot
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| *[[Primary biliary cirrhosis]]
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| *[[Refsum's Disease]]
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| *[[Rheumatoid Arthritis]]
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| *[[Sarcoidosis]]
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| *[[Scleroderma]]
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| *[[Sjogren's Syndrome]]
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| *Spinal process
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| *[[Spotted Fever]]
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| *[[Sprue]]
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| *[[Syphillis]]
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| *[[Systemic Lupus Erythematosus]]
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| *[[Thiamine deficiency]]
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| *[[Trauma]]
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| *[[Tuberculosis]]
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| *[[Typhoid Fever]]
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| *Uremic/[[Chronic Renal Failure]]
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| *Viral [[Hepatitis]]
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| *[[Vitamin B1]] deficiency
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| *[[Vitamin B6]] deficiency
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| *[[Vitamin B12 deficiency]]
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| ===Complete Differential Diagnosis of the Causes of {{PAGENAME}}===
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| (By organ system)
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| {|style="width:80%; height:100px" border="1"
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| |style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" | '''Cardiovascular'''
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| |style="height:100px"; style="width:75%" border="1" bgcolor="Beige" | No underlying causes
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| |-bgcolor="LightSteelBlue"
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| | '''Chemical / poisoning'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Dermatologic'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Drug Side Effect'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Ear Nose Throat'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Endocrine'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Environmental'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Gastroenterologic'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Genetic'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Hematologic'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Iatrogenic'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Infectious Disease'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Musculoskeletal / Ortho'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Neurologic'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Nutritional / Metabolic'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Obstetric/Gynecologic'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Oncologic'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Opthalmologic'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Overdose / Toxicity'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Psychiatric'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Pulmonary'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Renal / Electrolyte'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Rheum / Immune / Allergy'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Sexual'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Trauma'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
| |
| | '''Urologic'''
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| |bgcolor="Beige"| No underlying causes
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| |-
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| |-bgcolor="LightSteelBlue"
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| | '''Miscellaneous'''
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| |bgcolor="Beige"| No underlying causes
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| |-
| |
| |}
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| == Signs and symptoms == | |
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| Symptoms are related to the type of affected nerve and may be seen over a period of days, weeks, or years. Muscle weakness is the most common symptom of motor nerve damage. Other symptoms may include painful cramps and fasciculations (uncontrolled muscle twitching visible under the skin), muscle loss, bone degeneration, and changes in the skin, hair, and nails. These more general degenerative changes also can result from sensory or autonomic nerve fiber loss.
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| Sensory nerve damage causes a more complex range of symptoms because sensory nerves have a wider, more highly specialized range of functions. Larger sensory fibers enclosed in myelin (a fatty protein that coats and insulates many nerves) register vibration, light touch, and position sense. Damage to large sensory fibers lessens the ability to feel vibrations and touch, resulting in a general sense of numbness, especially in the hands and feet. People may feel as if they are wearing gloves and stockings even when they are not. Many patients cannot recognize by touch alone the shapes of small objects or distinguish between different shapes. This damage to sensory fibers may contribute to the loss of reflexes (as can motor nerve damage). Loss of position sense often makes people unable to coordinate complex movements like walking or fastening buttons, or to maintain their balance when their eyes are shut.
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| Neuropathic pain is difficult to control and can seriously affect emotional well-being and overall quality of life. Neuropathic pain is often worse at night, seriously disrupting sleep and adding to the emotional burden of sensory nerve damage. Neuropathic pain is usually perceived as a steady burning and/or "pins and needles" and/or "electric shock" sensations and/or tickling. The difference is due to the fact that "ordinary" pain stimulates only pain nerves, while a neuropathy often results in the firing of both pain and non-pain (touch, warm, cool) sensory nerves in the same area, producing signals that the spinal cord and brain do not normally expect to receive.
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| Smaller sensory fibers without myelin sheaths transmit pain and temperature sensations. Damage to these fibers can interfere with the ability to feel pain or changes in temperature. People may fail to sense that they have been injured from a cut or that a wound is becoming infected. Others may not detect pains that warn of impending heart attack or other acute conditions. (Loss of pain sensation is a particularly serious problem for people with diabetes, contributing to the high rate of lower limb amputations among this population.) Pain receptors in the skin can also become oversensitized, so that people may feel severe pain (allodynia) from stimuli that are normally painless (for example, some may experience pain from bed sheets draped lightly over the body).
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| Symptoms of autonomic nerve damage are diverse and depend upon which organs or glands are affected. Autonomic nerve dysfunction can become life threatening and may require emergency medical care in cases when breathing becomes impaired or when the heart begins beating irregularly. Common symptoms of autonomic nerve damage include an inability to sweat normally, which may lead to heat intolerance; a loss of bladder control, which may cause infection or incontinence; and an inability to control muscles that expand or contract blood vessels to maintain safe blood pressure levels. A loss of control over blood pressure can cause dizziness, lightheadedness, or even fainting when a person moves suddenly from a seated to a standing position (a condition known as postural or orthostatic hypotension).
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| Gastrointestinal symptoms frequently accompany autonomic neuropathy. Nerves controlling intestinal muscle contractions often malfunction, leading to diarrhea, constipation, or incontinence. Many people also have problems eating or swallowing if certain autonomic nerves are affected.
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| Numbness is an abnormal sensation called [[dysesthesia]]s and [[allodynia]]s that occur either spontaneously or in reaction to external stimuli, and a characteristic form of pain, called neuropathic pain or neuralgia, that is qualitatively different from the ordinary [[Pain and nociception|nociceptive]] pain one might experience from stubbing a toe or hitting a finger with a hammer.
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| Those with diseases or dysfunctions of their [[peripheral nerve]]s can present with problems in any of the normal peripheral nerve functions.
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| In terms of sensory function, there are commonly ''loss of function'' (''negative'') symptoms, which include [[numbness]], [[tremor]], and [[encopresis|gait imbalance]].
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| ''Gain of function'' (''positive'') symptoms include [[tingling]], [[Pain and nociception|pain]], [[itch]]ing, [[crawling]], and [[paresthesia|pins and needles]]. Pain can become intense enough to require use of opiate drugs (i.e., morphine, oxycontin).
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| Skin can become so hypersensitive that patients are prohibited from having anything touch certain parts of their body, especially the feet. People with this degree of sensitivity cannot have a bed sheet touch their feet or wear socks or shoes, and eventually become housebound.
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| Motor symptoms include ''loss of function'' (''negative'') symptoms of weakness, [[fatigue (physical)|tiredness]], heaviness, and [[gait abnormality|gait abnormalities]]; and ''gain of function'' (''positive'') symptoms of [[cramps]], tremor, and [[fasciculation]]s.
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| There is also [[Pain and nociception|pain]] in the muscles (''[[myalgia]]''), cramps, ''etc''., and there may also be [[autonomic nervous system|autonomic]] dysfunction.
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| During [[physical examination]], those with generalized peripheral neuropathies most commonly have distal sensory or motor and sensory loss, though those with a [[pathology]] (problem) of the peripheral nerves may be perfectly normal; may show proximal weakness, as in some [[inflammatory]] [[neuropathy|neuropathies]] like [[Guillain-Barré syndrome]]); or may show focal sensory disturbance or weakness, such as in [[mononeuropathy|mononeuropathies]], [[radiculopathy|radiculopathies]] and plexopathies.
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| Common disorders of the peripheral nerves include ''focal entrapment neuropathies'' (''e.g.'', [[carpal tunnel syndrome]]), ''generalized peripheral neuropathies'' (''e.g.'', [[diabetic neuropathy]]), ''plexopathies'' (''e.g.'', [[brachial]] [[neuritis]]) and ''radiculopathies'' (''e.g.'', of [[cranial nerve]] VII; [[Facial nerve]]).
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| ==Diagnosis== | | ==Diagnosis== |
| | [[Peripheral neuropathy history and symptoms|History and Symptoms]] | [[Peripheral neuropathy physical examination|Physical Examination]]| [[Peripheral neuropathy laboratory findings|Laboratory Findings]] | [[Peripheral neuropathy CT|CT]] | [[Peripheral neuropathy MRI|MRI]] | [[Peripheral neuropathy other imaging findings|Other Imaging Findings]] | [[Peripheral neuropathy other diagnostic studies|Other Diagnostic Studies]] |
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| Diagnosing peripheral neuropathy is often difficult because the symptoms are highly variable. A thorough neurological examination is usually required and involves taking an extensive patient history (including the patient’s symptoms, work environment, social habits, exposure to any toxins, history of alcoholism, risk of HIV or other infectious disease, and family history of neurological disease), performing tests that may identify the cause of the neuropathic disorder, and conducting tests to determine the extent and type of nerve damage.
| | ==Treatment== |
| | | [[Peripheral neuropathy medical therapy|Medical Therapy]] | [[Peripheral neuropathy surgery|Surgery]] | [[Peripheral neuropathy primary prevention|Primary Prevention]] | [[Peripheral neuropathy cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Peripheral neuropathy future or investigational therapies|Future or Investigational Therapies]] |
| ===Physical Examination===
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| A general physical examination and related tests may reveal the presence of a systemic disease causing nerve damage. Blood tests can detect diabetes, vitamin deficiencies, liver or kidney dysfunction, other metabolic disorders, and signs of abnormal immune system activity. An examination of cerebrospinal fluid that surrounds the brain and spinal cord can reveal abnormal antibodies associated with neuropathy. More specialized tests may reveal other blood or cardiovascular diseases, connective tissue disorders, or malignancies. Tests of muscle strength, as well as evidence of cramps or fasciculations, indicate motor fiber involvement. Evaluation of a patient’s ability to register vibration, light touch, body position, temperature, and pain reveals sensory nerve damage and may indicate whether small or large sensory nerve fibers are affected.
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| Based on the results of the neurological exam, physical exam, patient history, and any previous screening or testing, additional testing may be ordered to help determine the nature and extent of the neuropathy.
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| ===Computed Tomography===
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| Computed tomography, or CT scan, is a noninvasive, painless process used to produce rapid, clear two-dimensional images of organs, bones, and tissues. X-rays are passed through the body at various angles and are detected by a computerized scanner. The data is processed and displayed as cross-sectional images, or "slices," of the internal structure of the body or organ. Neurological CT scans can detect bone and vascular irregularities, certain brain tumors and cysts, herniated disks, encephalitis, spinal stenosis (narrowing of the spinal canal), and other disorders.
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| ===Magnetic resonance imaging===
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| Magnetic resonance imaging (MRI) can examine muscle quality and size, detect any fatty replacement of muscle tissue, and determine whether a nerve fiber has sustained compression damage. The MRI equipment creates a strong magnetic field around the body. Radio waves are then passed through the body to trigger a resonance signal that can be detected at different angles within the body. A computer processes this resonance into either a three-dimensional picture or a two-dimensional "slice" of the scanned area.
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| ===Electromyography===
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| Electromyography (EMG) involves inserting a fine needle into a muscle to compare the amount of electrical activity present when muscles are at rest and when they contract. EMG tests can help differentiate between muscle and nerve disorders.
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| ===Nerve conduction velocity===
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| Nerve conduction velocity (NCV) tests can precisely measure the degree of damage in larger nerve fibers, revealing whether symptoms are being caused by degeneration of the myelin sheath or the axon. During this test, a probe electrically stimulates a nerve fiber, which responds by generating its own electrical impulse. An electrode placed further along the nerve’s pathway measures the speed of impulse transmission along the axon. Slow transmission rates and impulse blockage tend to indicate damage to the myelin sheath, while a reduction in the strength of impulses is a sign of axonal degeneration.
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| ===Nerve biopsy===
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| Nerve biopsy involves removing and examining a sample of nerve tissue, most often from the lower leg. Although this test can provide valuable information about the degree of nerve damage, it is an invasive procedure that is difficult to perform and may itself cause neuropathic side effects. Many experts do not believe that a biopsy is always needed for diagnosis.
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| ===Skin biopsy===
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| Skin biopsy is a test in which doctors remove a thin skin sample and examine nerve fiber endings. This test offers some unique advantages over NCV tests and nerve biopsy. Unlike NCV, it can reveal damage present in smaller fibers; in contrast to conventional nerve biopsy, skin biopsy is less invasive, has fewer side effects, and is easier to perform.
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| ==Treatment of neuropathic pain== | |
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| Neuropathic pain can be very difficult to treat. Sometimes strong [[opioid]] analgesics may provide only partial relief. Opioid analgesics are to be considered only as a tertiary treatment. Several classes of medications not normally thought of as analgesics are often effective, alone or in combination with opioids and other treatments. These include [[tricyclic antidepressant]]s such as [[amitriptyline]] (Elavil®), [[anticonvulsant]]s such as [[gabapentin]] (Neurontin®) and [[pregabalin]] (Lyrica®).
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| In animal models of neuropathic pain it has been found that compounds which only block serotonin reuptake do not improve neuropathic pain.<!--
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| --><ref>{{cite journal |author=Bennett G, Xie Y |title=A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man |journal=Pain |volume=33 |issue=1 |pages=87-107 |year=1988 |pmid=2837713}}</ref><!--
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| --><ref>{{cite journal |author=Seltzer Z, Dubner R, Shir Y |title=A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury |journal=Pain |volume=43 |issue=2 |pages=205-18 |year=1990 |pmid=1982347}}</ref><!--
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| --><ref>{{cite journal |author=Kim S, Chung J |title=An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat |journal=Pain |volume=50 |issue=3 |pages=355-63 |year=1992 |pmid=1333581}}</ref><!--
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| --><ref>{{cite journal |author=Malmberg A, Basbaum A |title=Partial sciatic nerve injury in the mouse as a model of neuropathic pain: behavioral and neuroanatomical correlates |journal=Pain |volume=76 |issue=1-2 |pages=215-22 |year=1998 |pmid=9696476}}</ref><!--
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| --><ref>{{cite journal |author=Sung B, Na H, Kim Y, Yoon Y, Han H, Nahm S, Hong S |title=Supraspinal involvement in the production of mechanical allodynia by spinal nerve injury in rats |journal=Neurosci. Lett. |volume=246 |issue=2 |pages=117-9 |year=1998 |pmid=9627194}}</ref><!--
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| --><ref>{{cite journal |author=Lee B, Won R, Baik E, Lee S, Moon C |title=An animal model of neuropathic pain employing injury to the sciatic nerve branches |journal=Neuroreport |volume=11 |issue=4 |pages=657-61 |year=2000 |pmid=10757496}}</ref><!--
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| --><ref>{{cite journal |author=Decosterd I, Woolf C |title=Spared nerve injury: an animal model of persistent peripheral neuropathic pain |journal=Pain |volume=87 |issue=2 |pages=149-58 |year=2000 |pmid=10924808}}</ref><!--
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| --><ref>{{cite journal |author=Vadakkan K, Jia Y, Zhuo M |title=A behavioral model of neuropathic pain induced by ligation of the common peroneal nerve in mice |journal=The journal of pain : official journal of the American Pain Society |volume=6 |issue=11 |pages=747-56 |year=2005 |pmid=16275599}}</ref>
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| Similarly, compounds that only block [[norepinephrine]] reuptake also do not improve neuropathic pain. Compounds such as [[duloxetine]], [[venlafaxine]], and [[milnacipran]] that block both [[serotonin]] reuptake and norepinephrine reuptake do improve neuropathic pain.
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| Antidepressants usually reduce neuropathic pain more quickly and with smaller doses than they relieve depression. Antidepressants therefore seem to work differently
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| on neuropathic pain than on depression, perhaps by activating descending norepinephrinergic and serotonergic pathways in the spinal cord that block pain signals from ascending to the brain.
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| Many of the pharmacologic treatments for chronic neuropathic pain decrease the sensitivity of [[nociceptive]] receptors, or desensitize [[C fibers]] such that they transmit fewer signals. The newer anticonvulsants gabapentin and pregabalin appear to work by blocking calcium channels in damaged peripheral neurons. Tricyclic antidepressants may also work on sodium channels in peripheral nerves. The anticonvulsants [[carbamazepine]] (Tegretol®) and [[oxcarbazepine]] (Trileptal®), especially effective
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| on [[trigeminal neuralgia]], are thought to work principally on [[sodium channels]].
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| In general, the antidepressants seem to be most effective on continuous burning pain, while the anticonvulsants seem to
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| work best on sudden, lancinating, "shock-like" pains that appear to involve large numbers of peripheral nerves improperly firing together.
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| In some forms of neuropathy, especially post-herpes neuralgia, the topical application of local anesthetics such as [[lidocaine]] can provide relief. A transdermal patch containing 5% [[lidocaine]] is available. [[Ketamine]] in a transdermal gel is also frequently effective when the neuropathy is localized. Neurontin 100mg/g PLO gel is also effective for treating peripheral neuropathy, including [[Carpal Tunnel Syndrome]]. [[Capsaicin]] cream can be beneficial in several neurogenic pain disorders, which causes release of the pain neurotransmitter [[Substance P]], and eventually reduces the availability of Substance P.
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| [[Transcutaneous electrical nerve stimulation]] (TENS) is worth a trial in chronic neurogenic pain. Some pain management specialists will try acupuncture, with variable results. TENS, with certain electrical waveforms, appears to have an acupuncture-like function.
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| In some neuropathic pain syndromes, "crosstalk" occurs between descending sympathetic nerves and ascending sensory nerves. Increases in sympathetic nervous system activity result in an increase of pain; this is known as sympathetically-mediated pain. Reducing the sympathetic nerve activity in the painful region with local nerve blocks or systemic medications such as the [[alpha-blocker]] [[clonidine]] may provide relief. Other drugs, known for their ability to desensitize cardiac tissue, include [[beta-blockers]] such as [[propanolol]] and [[calcium channel blockers]] such as [[verapamil]].
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| The [[NMDA receptor]] seems to play a major role in neuropathic pain and in the development of opioid tolerance, and many experiments in both animals and humans have established that NMDA [[Receptor antagonist|antagonists]] such as [[ketamine]] and [[dextromethorphan]] can alleviate neuropathic pain and reverse opioid tolerance. Unfortunately, only a few NMDA antagonists are clinically available and their use is usually associated with unacceptable side effects.
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| Several opioids, particularly [[methadone]], have NMDA antagonist activity in addition to their μ-opioid agonist properties that seems to make them effective against neuropathic pain, although this is still the subject of intensive research and clinical study. Methadone has this property because it is a [[racemic]] mixture; one stereo-isomer is a μ-opioid agonist; the other is a NMDA antagonist.
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| A recent study showed smoking [[marijuana]] is beneficial in treating HIV-associated periphial <!--sp?
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| -->neuropathy.<ref>{{cite journal |author=Abrams D, Jay C, Shade S, Vizoso H, Reda H, Press S, Kelly M, Rowbotham M, Petersen K |title=Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial |journal=Neurology |volume=68 |issue=7 |pages=515-21 |year=2007 |pmid=17296917}}</ref>
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| In addition to pharmacological treatment there are several other modalities that help some cases. While lacking double blind trials, these have shown to reduce pain and improve patient quality of life particularly for chronic neuropathic pain: Interferential Stimulation; [[Acupuncture]]; [[Meditation]]; [[Cognitive Therapy]]; and prescribed exercise.
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| In more recent years, infrared photo therapy has been used to treat neuropathic symptoms. Photo therapy devices emit near [[infrared light]] typically at a wavelength of 890nm. This wavelength is believed to stimulate the release of [[nitric oxide]], an [[endothelium-derived relaxing factor]] into the bloodstream, thus vasodilating the capilaries and venuoles in the microcirculatory system. This increase in circulation has been shown effective in various clinical studies, to decrease pain and improve sensation in [[diabetes|diabetic]] and non-diabetic patients. Note that the U.S. [[FDA]] has not approved any infrared photo therapy devices to treat neuropathy.<ref>http://www.healthlight.stirsite.com/page/page/2909659.htm</ref>
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| ==Alternative medicine treatments==
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| There are 2 dietary supplements that have clinical evidence showing them to be effective treatments of diabetic neuropathy; alpha lipoic acid and benfotiamine. In several studies using a variety of dosages and routes of administration, [[alpha lipoic acid]] was found to reduce the various symptoms of peripheral diabetic neuropathy. A recent review of the published data determined “ALA should be considered as a treatment option for patients with peripheral diabetic neuropathy.” Also a recent study using orally administered alpha lipoic acid found that 600 mg once a day caused a marked reduction in the symptoms of diabetic neuropathy including stabbing pain, burning pain, paresthesia, and asleep numbness of the feet.
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| [[Benfotiamine]] is a lipid soluble form of thiamine that has several placebo controlled double blind trials proving efficacy in treating neuropathy and various other diabetic comorbidities. 400 mg a day was the most commonly studied dose.
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| ==See also==
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| *[[Nerve]]
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| *[[Peripheral nervous system]]
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| *[[Neuritis]]
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| *[[Neuralgia]]
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| *[[Small fiber peripheral neuropathy]]
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| *[[Phantom limb]]
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| *[[Phantom pain]]
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| *[[Posterior Rami Syndrome]]
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| *[[Neuropathy]]
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| *[[Myopathy]]
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| *[[Myelinopathy]]
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| *[[Guillain-Barré syndrome]]
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| ==References== | | == Case Studies == |
| {{Reflist|2}}
| | [[Peripheral neuropathy case study one|Case #1]] |
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| ==Additional Resources== | | ==Neuropathy Related Organizations== |
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| * [http://www.dellon.com/content/view/32/5/ Dr. Lee Dellon: Pioneering Pain Relief] '''''Dr. Lee Dellon's''''' research in the pain caused by Peripheral Neuropathy and other nerve disorders is highlighted in this recent article.
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| ==Neuropathy related organizations==
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| * [http://www.neupsig.org/ Special Interest Group on Neuropathic Pain]of the [http://www.iasp-pain.org International Association for the Study of Pain (IASP)] | | * [http://www.neupsig.org/ Special Interest Group on Neuropathic Pain]of the [http://www.iasp-pain.org International Association for the Study of Pain (IASP)] |
| *[http://www.neuropathy.org/site/PageServer The Neuropathy Association] | | *[http://www.neuropathy.org/site/PageServer The Neuropathy Association] |
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| ==External links== | | ==External Links== |
| * [http://www.nepknowmore.ca/ Nep Know More Provides Additional Help and Information on Neuropathic Pain]
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| *[http://www.loftusmd.com/Articles/Pain/overview.html A neuropathic series of articles from a neurologist who researches neuropathic pain] | | *[http://www.loftusmd.com/Articles/Pain/overview.html A neuropathic series of articles from a neurologist who researches neuropathic pain] |
| * [http://www.celiac.com/st_prod.html?p_prodid=842 Up to 16% of Patients with Small Fiber Neuropathy May Have Celiac Disease]
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| * [http://diabetes.niddk.nih.gov/ National Diabetes Information Clearinghouse]
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| * [http://www.mapinc.org/drugnews/v07/n260/a03.html Information about Neurology Article on marijuana's effect on neuropathic pain] | | * [http://www.mapinc.org/drugnews/v07/n260/a03.html Information about Neurology Article on marijuana's effect on neuropathic pain] |
| * [http://www.diabetesincontrol.com/annodyne/burkeseries.php Nitric Oxide and its Role in Diabetes, Wound Healing and Peripheral Neuropathy]
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| * [http://diabetes.niddk.nih.gov/ National Diabetes Information Clearinghouse]
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| == Acknowledgements ==
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| The content on this page was first contributed by: C. Michael Gibson, M.S., M.D.
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