The general cause of this disease appears to be prolonged and heavy consumption of alcohol accompanied by a nutritional deficiency. However there is ongoing debate over the active mechanisms, including whether the main cause is the direct toxic effect of alcohol itself or whether the disease is a result of<unk> m-related malnutrition. A 2019 metastudy found that the relationship between ethanol toxicity and neuropathy remained unproven. Effects due to nutritional deficiency Frequently<unk> s have disrupted social links in their lives and have an irregular lifestyle. This may cause an<unk>  to change their eating habits including more missed meals and a poor dietary balance.<unk> m may also result in loss of appetite,<unk>  gastritis, and vomiting, which decrease food intake. Alcohol abuse damages the lining of the gastrointestinal system and reduces absorption of nutrients that are taken in. The combination of all of them may result in a nutritional deficiency that is linked to the development of<unk> . There is evidence that providing individuals with adequate vitamins improves symptoms despite continued alcohol intake, indicating that vitamin deficiency may be a major factor in the development and progression of<unk> . In experimental models of<unk>  utilizing rats and monkeys no convincing evidence was found that proper nutritional intake along with alcohol results in polyneuropathy. Thiamine pyrophosphate structure. As a result of nutritional deficiency in those with<unk> , low thiamine levels are usually present and have been proposed as a cause of the nerve destruction. In most cases, individuals with<unk>  have some degree of nutritional deficiency. Alcohol, a carbohydrate, increases the metabolic demand for thiamine (vitamin B1) because of its role in the metabolism of glucose. Thiamine levels are usually low in<unk> s due to their decreased nutritional intake. In addition, alcohol interferes with intestinal absorption of thiamine, thereby further decreasing thiamine levels in the body. Thiamine is important in three reactions in the metabolism of glucose: the decarboxylation of pyruvic acid, d-ketoglutaric acid, and transketolase. A lack of thiamine in the cells may therefore prevent neurons from maintaining necessary adenosine triphosphate (ATP) levels as a result of impaired glycolosis. Thiamine deficiency alone could explain the impaired nerve conduction in those with<unk> , but other factors likely play a part. The malnutrition many<unk> s suffer deprives them of important cofactors for the oxidative metabolism of glucose. Neural tissues depend on this process for energy, and disruption of the cycle would impair cell growth and function. Schwann cells produce myelin that wraps around the sensory and motor nerve axons to enhance action potential conduction in the periphery. An energy deficiency in Schwann cells would account for the disappearance of myelin on peripheral nerves, which may result in damage to axons or loss of nerve function altogether. In peripheral nerves, oxidative enzyme activity is most concentrated around the nodes of Ranvier, making these locations most vulnerable to cofactor deprivation. Lacking essential cofactors reduces myelin impedance, increases current leakage, and slows signal transmission. Disruptions in conductance first affect the peripheral ends of the longest and largest peripheral nerve fibers because they suffer most from decreased action potential propagation. Thus, neural deterioration occurs in an accelerating cycle: myelin damage reduces conductance, and reduced conductance contributes to myelin degradation. The slowed conduction of action potentials in axons causes segmental demyelination extending proximally; this is also known as retrograde degeneration. Many of the studies conducted that observe<unk>  in patients are often criticized for their criteria used to assess nutritional deficiency in the subjects because they may not have completely ruled out the possibility of a nutritional deficiency in the genesis of the polyneuropathy. Many researchers favor the nutritional origin of this disease, but the possibility of alcohol having a toxic effect on the peripheral nerves has not been completely ruled out. Effects due to alcohol ingestion The consumption of alcohol may lead to the buildup of certain toxins in the body. For example, in the process of breaking down alcohol, the body produces acetaldehyde, which can accumulate to toxic levels in<unk> s. This suggests that there is a possibility ethanol (or its metabolites) may cause<unk> . There is evidence that polyneuropathy is also prevalent in well nourished<unk> s, supporting the idea that there is a direct toxic effect of alcohol. The metabolic effects of liver damage associated with<unk> m may also contribute to the development of<unk> . Normal products of the liver, such as lipoic acid, may be deficient in<unk> s. This deficiency would also disrupt glycolosis and alter metabolism, transport, storage, and activation of essential nutrients. Acetaldehyde is toxic to peripheral nerves. There are increased levels of acetaldehyde produced during ethanol metabolism. If the acetaldehyde is not metabolized quickly the nerves may be affected by the accumulation of acetaldehyde to toxic levels.
Alcoholic polyneuropathy
Tropical neuropathy
Diabetic neuropathy
Critical illness polyneuropathy
Chronic inflammatory demyelinating polyneuropathy
Paraneoplastic cerebellar degeneration
Vasculitic neuropathy
Polyneuropathy