Alcoholic Neuropathy 

Updated: Feb 01, 2021
Author: Scott R Laker, MD; Chief Editor: Robert H Meier, III, MD 

Overview

Practice Essentials

The development of peripheral neuropathy, specifically the formation of primary axonal sensorimotor peripheral polyneuropathy, is a risk for persons with a history of chronic consumption of large volumes of alcohol. Symptoms of alcoholic neuropathy, like those of many of the other axonal mixed polyneuropathies, manifest initially in the distal lower extremities. Sensory symptoms (eg, numbness, paresthesias, dysesthesias, allodynia, and loss of vibration and position sense) generally manifest prior to motor symptoms (eg, weakness). However, patients may present with both motor and sensory symptoms at initial presentation.[1, 2]

In most cases of alcoholic neuropathy, the onset of the polyneuropathy is insidious and prolonged, but some cases have been associated with acute, rapidly progressive onset.[3] Symptoms seem to be associated with the lifetime consumption of alcohol, although exceptions are common. Severe cases of alcoholic neuropathy can lead to the development of symptoms in the proximal lower extremities and distal upper extremities.[4]

Signs and symptoms of alcoholic neuropathy

Classic physical examination findings associated with alcoholic neuropathy may include the following:

  • Diminished sensation to vibration or pinprick stimulation in a "stocking-to-glove" distribution
  • Thermal and proprioceptive sensation abnormalities
  • Muscle stretch reflexes, especially of the gastrocnemius-soleus muscle complex
  • Weakness of ankle/toe dorsiflexion and/or ankle plantar flexion strength
  • Intrinsic atrophy of foot muscles in advanced cases
  • Gait ataxia with a widened base of support or bilateral foot drop
  • Patellar and Achilles deep tendon reflexes are often reduced or absent

Workup in alcoholic neuropathy

The following laboratory studies are indicated:

  • Chemistry profile
  • Diabetes testing
  • Creatinine level
  • Thiamine, vitamin B-12, and folic acid levels [5]

The following laboratory tests are ordered once more common diagnoses are essentially excluded:

  • Heavy metal toxicity
  • Erythrocyte sedimentation rate
  • Human immunodeficiency virus (HIV) infection and venereal disease

Other tests include the following:

  • Nerve conduction studies (NCSs)
  • Needle electromyography (EMG)
  • Vibrometer testing

Management of alcoholic neuropathy

Comprehensive physical therapy for patients with alcoholic neuropathy may include the following:

  • Gait and balance training, possibly with an assistive device for safety
  • Range of motion (ROM) exercises and stretching, particularly for the gastrocnemius-soleus muscle, to prevent contracture and maintain normal gait mechanics
  • Strength training of weakened muscles

If liver damage is evident, appropriate consultation with a transplantation service is recommended. However, neuropathy is generally an exclusion criterion for transplantation.

An ankle-foot orthosis (AFO) may be needed to assist patients with weak ankle dorsiflexion, eversion, and/or plantar flexion. This device also can help with ankle proprioception and can improve gait and prevent ankle sprains. Vigilant foot care and the use of shoes with an enlarged toe box are useful in preventing foot ulcers.

Pathophysiology

Alcoholic neuropathy is a primary axonal neuropathy characterized by wallerian degeneration of the axons and a reduction in the myelination of neural fibers.[6] Controversy surrounds the pathogenic role of alcohol in development of this neuropathy. Studies on rat models have indicated that alcohol does have a directly neurotoxic effect on spinal cord and neuronal organelles.[7, 8] Acetaldehyde, a metabolite of ethanol (ETOH), has a direct neurotoxic effect. Ethanol also impairs axonal transport and disturbs cytoskeletal properties.

A review of the human literature implicates nutritional deficiencies, most often thiamine deficiency, that are common in alcoholic patients, as commonly accompanying complicating factors in the development of this neuropathy. Persons with alcoholism may consume smaller amounts of essential nutrients and vitamins and/or exhibit impaired gastrointestinal absorption of these nutrients secondary to the direct effects of alcohol.

Protein kinases A and C have also been implicated in the painful symptoms associated with alcoholic neuropathy.[9] Symptoms also have an association with the metabotropic glutamate 5 (mGlu5) receptor in rat models.[10]

Attention has been paid to the hypothesis that alcoholic neuropathy is a result, in part, of increased oxidative stress leading to free radical damage to nerves. Ethanol has been shown to promote oxidative stress by decreasing the concentration of endogenous antioxidants[11] and by generating reactive oxygen species and increasing lipid peroxidation.[12]

A study by Behl et al also indicates that oxidative stress is associated with alcoholic neuropathy. According to the investigators, such stress may play a role in the activation of matrix metalloproteinases (MMPs), leading to a disruption in the blood-brain barrier. Consequently, chronic alcohol consumption would result in downregulation of central nervous system receptors.[13]

An understanding of alcohol’s potential to increase oxidative stress has led some researchers to investigate the use of antioxidants as a therapy for alcohol-induced neuropathy. In one recent study, curcumin, an alkaloid isolated from Curcuma longa, was shown to produce significant protection from alcoholic neuropathy in a rat model, demonstrated by improved motor nerve conduction velocity and reduction in nociception.[14] This protective effect of curcumin may be accounted for by a reduction in oxidative stress, inhibition of cytokines, and a decrease in DNA fragmentation. Another study demonstrated that in a rat model, tocotrienol, an isoform of vitamin E, given after the development of alcoholic neuropathy may be neuroprotective via its antioxidant properties.[15]

It has also been suggested that alcohol-induced neuropathy may be in part caused by molecular and signal transduction abnormalities involving insulin and insulinlike growth factor.[16]

Thiamine, also known as the antiberiberi factor or antineuritic factor, is an essential vitamin in the metabolism of pyruvate and has a role in the health of the peripheral nervous system. Thiamine deficiency is commonly found in alcoholic patients, due to decreased absorption and hepatic depletion. Other studies have linked the direct toxic effects of alcohol on peripheral nerves with development of neuropathy. A combination of nutritional deficiency and direct toxicity is likely involved in the pathogenesis of alcoholic neuropathy, and these effects may be additive.[17, 18] Alcohol also has been implicated in the development of cardiac autonomic neuropathy (CAN) and various cranial neuropathies, including optic neuropathy and vagus neuropathy.

Pure alcoholic neuropathy is distinguishable from beriberi (thiamine deficiency). A histopathological review of sural nerve biopsy results revealed small-fiber axonal loss, myelin irregularities, and possibly neural regeneration in chronic cases.[17, 18] A Japanese study found an alcoholic dehydrogenase gene mutation that led to decreased alcohol metabolism and decreased sensory nerve action potentials in the affected group.[19]

A study by Michalak et al found that although erythrocyte transketolase activity, which is associated with thiamine status, was decreased in subjects with diabetic neuropathy, there was only a trend toward the decrease of such activity, compared with healthy controls, in patients with alcoholic neuropathy. The study involved 29 patients with type 2 diabetes mellitus and 31 patients with a history of alcohol dependence, all of whom demonstrated signs and symptoms of neuropathy. Assessment of thiamine pyrophosphate did not reveal thiamine deficiency in either the diabetic neuropathy or alcoholic neuropathy groups.[20]

Epidemiology

Frequency

A literature review by Julian et al reported that in chronic alcohol abusers, the prevalence of peripheral neuropathy is 46.3%.[21]

United States

Of all the deleterious effects of excessive alcohol consumption, neuropathy is the most common. The true incidence of alcoholic neuropathy in the general population is unknown, and figures vary widely depending on the definition of chronic alcoholism and the criteria used to detect and classify neuropathy. Using the criteria for alcoholism listed in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), studies employing clinical and electrodiagnostic criteria have estimated, similar to the above-mentioned report by Julian et al, that neuropathy is present in 25-66% of defined "chronic alcoholics."

Mortality/Morbidity

Chronic consumption of alcohol has been implicated in end-organ damage to multiple systems. Damaged structures include the brain (exhibited by development of Wernicke encephalopathy, Korsakoff psychosis, and cerebellar ataxia), heart (as in cardiac myopathy and autonomic neuropathy), pancreas, gallbladder, and liver (cirrhosis), as well as the peripheral nerves. Patients with multisystem damage as a result of alcohol consumption often die of cardiac or liver failure.

Children exposed to greater than 2 oz of alcohol per day in utero exhibit nerve conduction slowing and decreased compound muscle action potential (CMAP) amplitude in comparison with children with no prenatal exposure to alcohol.[22]

Race

Cultural and racial factors involved in the consumption of alcoholic beverages are beyond the scope of this article. The subject has not been well studied in terms of the development of alcoholic neuropathy. However, one noteworthy study suggested that the risk of developing peripheral neuropathy is higher in alcoholic patients whose parents had a history of alcoholism.[23]

Sex

Ammendola and colleagues conducted a study to assess differences between men and women in the development of alcoholic neuropathy.[24] This study used the sural sensory nerve action potential (SNAP) amplitude (ie, nerve conduction study) as the variable measure to detect significant neuropathy in a population of males and females with chronic alcoholism. Although the study provided control for nutritional deficiencies, the female group with chronic alcoholism had a significantly lower sural SNAP amplitude compared with the male group with similar total lifetime dose of ethanol consumption (TLDEC). This study suggested that females may demonstrate increased sensitivity to the toxic effects of alcohol on peripheral nerves.

Age

Most patients diagnosed with alcoholic neuropathy are aged 40-60 years. As mentioned previously, development of alcoholic neuropathy is associated with the duration and extent of total lifetime consumption of alcohol. Elderly persons, because of the natural diminution of postural reflexes and the nerve cell degeneration that occurs with advanced age, may be more at risk for the clinical problems associated with a peripheral neuropathy, such as frequent falls and loss of balance.

 

Presentation

History

Ascertaining the symptomatic history of a patient with alcoholic neuropathy is not specific for diagnosis. Pure alcoholic neuropathy is characterized by a progressive, sensory-dominant symptomatology. Interestingly, concomitant thiamine deficiency creates a much more variable presentation. A detailed history of alcohol use should be obtained from any patient presenting with symptoms of general neuropathy. Additionally, nutritional history and questioning regarding other neuropathy risk factors should be documented.[25]

Patients with alcoholic neuropathy typically present with a history of chronic consumption of alcohol and an insidious onset of distal lower extremity paresthesias, dysesthesias, or weakness. The most common presenting complaint seems to be paresthesias in the feet and toes. Over time, these symptoms usually progress proximally and symmetrically. Less commonly, patients present with a more rapid, acute onset of symptoms.

Patients also may have a history of gait ataxia and difficulty walking or a history of frequent falls.

In cases of more severe and advanced presentation, patients may report distal upper extremity symptoms.

In rare cases, vagus or recurrent laryngeal nerve involvement has been described. These patients may present with hoarseness and a weak voice.

Physical

Classic physical examination findings associated with alcoholic neuropathy may include the following:

  • Diminished sensation to vibration or pinprick stimulation in a "stocking-to-glove" distribution

  • Thermal and proprioceptive sensation abnormalities

  • Muscle stretch reflexes, especially of the gastrocnemius-soleus muscle complex

  • Weakness of ankle/toe dorsiflexion and/or ankle plantar flexion strength

  • Intrinsic atrophy of foot muscles in advanced cases

  • Gait ataxia with a widened base of support or bilateral foot drop

  • Patellar and Achilles deep tendon reflexes are often reduced or absent

Evidence of other alcohol-related end-organ damage also may be observed on physical examination. The patient should be examined for additional manifestations of chronic alcohol abuse such as caput medusae, ascites, digital clubbing, Dupuytren contractures, palmar erythema, gynecomastia, and jaundice.

Causes

Excess alcohol consumption causes alcoholic neuropathy. The factors most directly associated with the development of alcoholic neuropathy include the duration and amount of total lifetime alcohol consumption. Indeed, the aforementioned literature review by Julian et al indicated that total lifetime ethanol dose is the greatest risk factor for alcohol-related peripheral neuropathy. Genetics also play a role, according to the study, as do male gender and the type of alcohol ingested.[21]

As previously stated, further studies must be performed to determine genetic influences on this disorder.

 

DDx

Differential Diagnoses

 

Workup

Laboratory Studies

The following laboratory studies are indicated:

  • Chemistry profile - Chronic alcohol consumption may cause an increase in liver enzyme levels (eg, aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase).

  • Diabetes testing - Peripheral neuropathy may be among the first presenting symptoms associated with diabetes mellitus (DM); however, the majority of electromyographically diagnosed diabetic peripheral polyneuropathies occur in patients with long-standing histories of diabetes mellitus. Hemoglobin A1C can be used to estimate average blood glucose levels over the course of previous months.

  • Creatinine level - Renal insufficiency indicated by elevated blood creatinine levels also may be a cause for peripheral neuropathy.

  • Thiamine, vitamin B-12, and folic acid levels - These essential vitamins play an important role in the proper functioning of the peripheral and central nervous systems and should be the among the first laboratory tests ordered on a patient with polyneuropathy. Nutritional deficiencies associated with alcoholism are common and may contribute to the development of neuropathy in alcoholic patients (see Pathophysiology).[5]

The following laboratory tests are ordered once more common diagnoses are essentially excluded:

  • Screen for heavy metal toxicity. The toxicity of lead and other heavy metals is a well-known cause of neuropathy.

  • Determine the erythrocyte sedimentation rate. It may be elevated in patients with symptoms of a peripheral polyneuropathy, owing to an inflammatory condition (eg, paraneoplastic syndrome).

  • Test for human immunodeficiency virus (HIV) infection and venereal disease. Distal symmetric polyneuropathy is a common complication of HIV disease and can be an early manifestation of HIV infection.[26] Recent research suggests that HIV-infected patients who use illicit substances such as alcohol are at a higher risk for developing distal symmetric polyneuropathy.[27] Syphilis should also be considered as a cause of neuropathy.

Imaging Studies

Radiographic evidence of distal neuropathic arthropathy may also be present as a result of long-term sensory deficits.

Other Tests

Nerve conduction studies (NCSs)

Although not specific for alcoholic neuropathy, NCSs can help to clarify the diagnosis and can to some extent quantify the amount of peripheral neuropathy present, when comparisons are made with age-adjusted normal values. However, nerve conduction velocities (NCVs) are generally normal or mildly slowed in patients with alcoholic neuropathy. Some fast-conducting axons can be spared, preserving measured velocity until axon loss has severely progressed. Demyelinating neuropathies show a greater loss of conduction velocity. Note the following:

  • Sural/superficial peroneal SNAP - In ethanol (ETOH) neuropathy, the response may be absent or the amplitude may be significantly reduced. The superficial peroneal SNAP generally is more difficult to obtain than is the sural in average patients, including elderly individuals; therefore, it is less specific for pathology. The sural SNAP should be readily obtainable in most patients, including those of advanced age.

  • Tibial/peroneal compound motor action potential (CMAP) and NCV to intrinsic foot muscle - In ETOH neuropathy, test results may show significantly reduced amplitude. Results may demonstrate slowing of NCV below the reference range.

  • Ulnar/median SNAP - Consider performing this test to evaluate the extent of neuropathy if lower extremity sensory studies suggest abnormalities.

  • Ulnar/median CMAP - Consider performing this test to evaluate the extent of neuropathy if lower extremity motor studies suggest abnormalities.

  • Tibial H-reflex - In ETOH neuropathy, the patient may have an absent response or may have symmetrically reduced amplitude or increased latency. Typically, this is thought to be the most sensitive of electrophysiologic tests, with some studies quoting rates as high as 50%.

  • T-wave - One study found that the T-wave is somewhat more sensitive for alcoholic neuropathy.[28]

Needle electromyography (EMG)

Needle EMG is based on presentation. A typical peripheral neuropathy screen will involve a proximal muscle and a distal one in the lower and upper extremities.

A more extensive screen also may be useful in evaluating for the presence of a concomitant lumbosacral radiculopathy.

Significant abnormalities seen in patients with ETOH neuropathy include the presence of positive sharp waves and/or fibrillation potentials. Complex, repetitive discharges also may be observed. However, if the NCSs are normal, the presence of positive sharp waves in 1 intrinsic foot muscle is not necessarily indicative of neuropathic pathology. Occasionally, intrinsic foot muscles display abnormal electromyographic potentials in asymptomatic people.

If lower extremity muscle abnormalities are detected, a sampling of upper extremity muscles is indicated to estimate extent of disease.

Vibrometer testing

Results may be useful in detecting early signs of subclinical neuropathic disease.

 

Treatment

Rehabilitation Program

Physical Therapy

Comprehensive physical therapy for patients with alcoholic neuropathy may include the following:

  • Gait and balance training, possibly with an assistive device for safety

  • Range of motion (ROM) exercises and stretching, particularly for the gastrocnemius-soleus muscle, to prevent contracture and maintain normal gait mechanics

  • Strength training of weakened muscles

Occupational Therapy

Occupational therapy also can be an important component of the rehabilitation process in individuals with alcoholic neuropathy. Various elements can be combined into a program to help the patient maximize function, including the following:

  • Training in performance of activities of daily living (ADL), with adaptive equipment if necessary

  • Compensatory strategies to accommodate for insensate or weakened limbs

Medical Issues/Complications

Home evaluations can be ordered to assess the safety, appropriateness, and functionality of the patient in the home.

Surgical Intervention

If liver damage is evident, appropriate consultation with a transplantation service is recommended. However, neuropathy is generally an exclusion criterion for transplantation.

Interestingly, there has been a case of liver transplantation resulting in resolution of alcoholic polyneuropathy, although the patient was also treated for nutritional and vitamin-deficiency polyneuropathy.[29]

Consultations

Consultation with a psychiatrist may be indicated to help patients with chronic alcoholism recover from the physical and emotional withdrawal associated with cessation of alcohol consumption.

Consultation with a nutritionist may be indicated to help formulate strategies for replacement of essential nutrients in malnourished alcoholic patients.

Referral to a substance abuse support group, such as Alcoholics Anonymous (AA), may help patients to cope with alcohol cessation.

Other Treatment

An ankle-foot orthosis (AFO) may be needed to assist patients with weak ankle dorsiflexion, eversion, and/or plantar flexion. This device also can help with ankle proprioception and can improve gait and prevent ankle sprains. Vigilant foot care and the use of shoes with an enlarged toe box are useful in preventing foot ulcers.

The use of warm or hot footbaths is a potential hazard in alcoholic neuropathy, because such treatment may cause burns to a patient with an insensate extremity.

 

Medication

Medication Summary

Painful dysesthesias associated with alcoholic neuropathy can be treated using gabapentin or amitriptyline as adjunct agents with other OTC pain medications, such as aspirin or acetaminophen.

Anticonvulsants

Class Summary

Use of certain antiepileptic drugs, such as the gamma aminobutyric acid (GABA) analogue gabapentin (Neurontin), has proven helpful in some cases of neuropathic pain. These drugs have central and peripheral anticholinergic effects, as well as sedative effects, and they block the active reuptake of norepinephrine and serotonin. The multifactorial mechanism of analgesia could include improved sleep, an altered perception of pain, and an increase in the pain threshold. Rarely should these drugs be used in the treatment of acute pain, because a few weeks may be required for them to become effective.

Gabapentin (Neurontin)

Gabapentin has anticonvulsant properties and antineuralgic effects; however, the exact mechanism of action is unknown. Gabapentin is structurally related to GABA but does not interact with GABA receptors.

Tricyclic antidepressants

Class Summary

These agents make up a complex group of drugs that have central and peripheral anticholinergic effects, as well as sedative effects. They have central effects on pain transmission and block the active reuptake of norepinephrine and serotonin.

Amitriptyline (Elavil)

Amitriptyline is an analgesic for certain chronic and neuropathic pain.

Analgesic, Topical

Class Summary

When used topically, capsaicin works through the depletion of substance P. It causes significant burning sensations when applied, and patients must be educated about this effect.

Capsaicin topical (Dolorac, Zostrix)

Capsaicin is a natural chemical derived from plants of the Solanaceae family. It penetrates deep for temporary relief of minor aches and pains of muscles and joints associated inflammatory reactions. It may render skin and joints insensitive to pain by depleting substance P in peripheral sensory neurons.

 

Follow-up

Further Outpatient Care

Encourage periodic follow-up visits to monitor for neuropathic progression, as well as to assess functional deficits and the effectiveness of prior interventions (eg, alcohol cessation, gait/balance training).

Deterrence

Cessation of alcohol consumption is necessary to improve or reverse the symptoms associated with alcoholic neuropathy. Attendance of support groups (eg, AA) or the use of pharmacologic intervention (disulfiram [Antabuse]) may be of benefit to the patient with alcoholic neuropathy. Unfortunately, disulfiram also can cause neuropathy. In fact, 1 in 15,000 patients taking disulfiram develops peripheral neuropathy every year due to disulfiram toxicity. These patients are often misdiagnosed as having alcoholic neuropathy.[30]

Complications

Complications of alcoholic neuropathy include morbidity associated with falls and gait ataxia, as well as the potential for thermal injuries, burns, and pressure ulcers. Multiple organ systems, including the heart and eyes, can be adversely affected by nerve damage associated with excessive alcohol consumption. Alcoholic cerebellar damage coupled with neuropathic impairment of proprioception in the legs can be devastating to a patient's gait pattern and can make independent ambulation impossible.

Prognosis

According to Dell and Guzewicz, the prognosis for the arresting or reversal of symptoms associated with alcoholic neuropathy is fair to good following cessation of drinking.[31]

A study by Di Ciaula et al found that sympathetic autonomic dysfunction occurring in chronic alcoholics improved after 12 months of abstinence, although, looking also at the gastrointestinal effects of alcoholism, the investigators determined that certain preabstinence problems, including dyspepsia and changes in gastric emptying and orocecal transit times, remained.[32]

Patient Education

Educate patients on how to protect themselves from the deleterious effects of alcoholic neuropathy on touch, gait, balance, and general strength. These patients should also be counseled on the need for rigorous skin checks of the lower extremities as a means of preventing ongoing morbidity.