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.
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.  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.
Alcoholic neuropathy is a primary axonal neuropathy characterized by wallerian degeneration of the axons and a reduction in the myelination of neural fibers.  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. [3, 4] 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.  Symptoms also have an association with the metabotropic glutamate 5 (mGlu5) receptor in rat models. 
Recently, 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  and by generating reactive oxygen species and increasing lipid peroxidation. 
This 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.  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. 
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. 
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. [12, 13] 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. [12, 13] 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. 
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. 
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 that neuropathy is present in 25-66% of defined "chronic alcoholics." The factors most directly associated with the development of alcoholic neuropathy include the duration and amount of total lifetime alcohol consumption.
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. 
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. 
Ammendola and colleagues conducted a study to assess differences between men and women in the development of alcoholic neuropathy.  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.
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.
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