Alcoholic polyneuropathy: causes of development and treatment methods

Constant consumption of strong drinks is the cause of the manifestation of a disease called alcoholic polyneuropathy. Timely detection such an illness is an opportunity to cure it. If the disease develops into a chronic stage, then the alcoholic may develop serious problems with the respiratory system, heart function, metabolic processes, and limited mobility. Therefore, close people need to monitor the condition of a person addicted to strong drinks. Otherwise, it will be very difficult to save him.

What it is?

Alcoholic polyneuropathy, whose ICD code is 10: G62.1, is called extensive damage to nerve cells by ethanol toxins. The pathology is diagnosed in people with chronic alcohol addiction. It happens in patients with acute ethyl poisoning.

Alcohol toxins have an extremely negative effect on the human nervous system. By destroying the myelin sheath and nerve fiber, they lead to all types of sensory disturbances. Such exposure leads to the development of alcoholic polyneuropathy, the symptoms of which suggest that this is an extremely serious disease that worsens the patient’s quality of life and leads to disability.

Characteristic signs of alcoholic polyneuropathy:

refers to complications of alcohol intoxication;
occurs more often in acute or subacute form;
multiple neuronal damage (affects the entire nervous system or large areas of the nervous system);
as a result of toxic effects, metabolism in neurons is disrupted;
metabolic disorder causes dysfunction of the peripheral and/or central autonomic nervous system;
damage to the nervous tissue of the central nervous system (in the brain and spinal cord) is rare;
a person loses his ability to work and receives group II disability;
with adequate treatment, ability to work is restored;
refusal of therapy ends in death.

According to statistics, severe alcoholic polyneuropathy develops in 30% of men and 10% of women with addiction. During a comprehensive examination of the body using electroneuromyography, damage to the nervous tissue is detected in all chronic alcoholics. That is, the frequency of occurrence is 97–100% in addicted people, but the disease occurs in a latent (asymptomatic) form.

Reference! Letts was the first in history to describe the symptoms of the disease in 1787 when he discovered neuropathy of alcoholic origin in patients with addiction.

general information

The disease, which is part of a group of neurological disorders, is called alcoholic polyneuropathy. It usually occurs at critical stages of addiction to strong drinks. The period of drinking alcohol is from 5 years or more. Signs of the disease were described in 1787 by the scientist Letts. Addiction to alcohol-containing products has an adverse effect on the entire body.

The disease affects the peripheral nervous system. A person experiences metabolic disorders , decreased sensitivity in the legs and arms. In accordance with international rules, when a disease is recorded in different countries, it is given a special label. For alcoholic polyneuropathy according to ICD 10, this is code G 62.1.

Causes

The metabolic process in neurons is disrupted by the toxic effects of ethyl alcohol and its breakdown products (metabolites, acetate) on the nerve cell. Polyneuropathy occurs in people with the last stage of chronic alcoholism or after prolonged heavy drinking. The disease can worsen due to hypothermia.

Alcoholic polyneuropathy can be triggered by:

consumption of low-quality alcoholic beverages;
inability of the body to neutralize toxins (genetic disorder, debility, old age, oncology);
vitamin deficiency, lack of useful micro- and macroelements;
deficiency of B vitamins or thiamine (B1) or folic acid (B9);
hepatitis, liver cirrhosis;
metabolic disorder.

Alcoholic polyneuropathy occurs in people without addiction if an excessive dose of alcohol is drunk or a fortified drink is consumed by a child or teenager. These are isolated cases, the pathogenesis is being studied. With a single ethanol intoxication, nervous system disorders remain due to self-medication or lack of medical care.

The essence of the disease

Pathological disorders consist in the destruction of the structures of the peripheral nervous system under the influence of toxic substances - the breakdown products of ethanol. Long-term exposure to alcohol leads to the destruction of neurons and their processes - axons. Alcohol also destroys vitamins and causes vitamin deficiency. Deficiency of thiamine and nicotinic acid is especially negative. Damaged tissue of peripheral nerve fibers and failure of metabolic processes cause specific sensations and symptoms of polyneuropathy.

Forms

The classification was based on the clinical manifestations of the disease. Multiple neuronal damage can be asymptomatic, acute, subacute and chronic. Depending on the type of alcoholic polyneuropathy, the patient is diagnosed with different symptoms and different treatments are prescribed. The first and last varieties occur with prolonged alcoholism, and the rest - in people with long-term drinking.

Forms of neuropathy according to clinical signs:

A type of alcoholic polyneuropathy	Distinctive features
Sensory	Defects in skin sensitivity in the extremities are detected. Accompanied by pain.
Motor	Characteristic disorder of reflex-motor function
Mixed (combined)	There are simultaneously signs of sensory and motor forms of polyneuropathy
Pseudotabetic (atactic)	Characterized by incoordination of movements, clinically similar to tabes spinal cord
Subclinical (initial)	There are no obvious disturbances: the neurons are just beginning to be damaged. Reflexes, motor skills and/or sensitivity are slightly impaired.
Vegetative	The cells of the ganglion (autonomic) nervous system, which regulates the body’s activities, are affected. Manifested by dysfunction of glands, blood vessels, and organs.

Polyneuropathy of the lower extremities

Most often, the pathological process affects the nerves and vessels of the lower extremities. Due to too much stress, they are the most vulnerable, so destructive disorders in the nerve fibers occur faster, leading to sensitivity disorders, pain, vascular diseases, and lameness. Alcoholic polyneuropathy of the lower extremities if left untreated can lead to severe complications due to which patients lose their ability to work and the ability to care for themselves.

Polyneuropathy of the upper extremities

Alcoholic polyneuropathy of the upper extremities occurs in patients with long-term addiction. It can also occur after a single use of large doses of ethanol. It is also accompanied by sensory and motor disturbances.

Reference! According to clinical signs, the forms are the same for all types of toxic damage to nervous tissue. There are no differences in dysfunctions of the nervous system in case of poisoning with alcohol, medicine, poison, or other harmful substance, so the cause is identified by tests.

Alcoholic polyneuropathy - what is it?

During the disease, different peripheral nerves are simultaneously affected. Men experience it more often than women. Usually the pathology proceeds sluggishly, but can clearly manifest itself after a binge or general hypothermia of the body. How long an alcoholic will be sick depends on several factors:

age;
alcoholic experience;
time to see a doctor;
willingness to completely abandon the use of alcoholic beverages;
individual characteristics of the body.

To quickly get rid of alcoholic polyneuropathy, the drugs should be taken for a long time. Additionally, you need to undergo physical therapy and lead a healthy lifestyle.

The disease is treated by neurologists and narcologists. They jointly examine the addict and draw up a comprehensive treatment and rehabilitation program for him.

Symptoms

Symptoms of neuropathy caused by alcohol intoxication depend on what form of the disease the patient has. The disease manifests itself as a disorder of the functions of the nervous system. If neurons in the spinal cord or brain are involved, signs of mixed autonomic polyneuropathy are more often observed. When the cells of the peripheral nervous system are damaged, the development of one type of disease is noted: sensory, motor, or combined.

General Neuropathy Clinic

Initially, a person notices pain in the nerve trunk and adjacent muscles, which intensifies with pressure. Later, paresthesia appears: a spontaneous feeling of goosebumps, tingling, burning in the limb.

Alcoholic polyneuropathy is often accompanied by:

decrease, memory loss;
mental disorders;
swelling of joints, feet, hands;
damage to the oculomotor, vagus, phrenic nerve;
impaired vision (alcoholic amblyopia), breathing, vascular function, and internal organs.

As it progresses, paralysis of the extensor or flexor muscles occurs. The affected muscles quickly atrophy. At the beginning of development, the reaction of tendon reflexes increases, then disappears or remains enhanced. The superficial sensitivity of the hands and/or feet changes from the fingers to the knees and elbows.

Alcoholic polyneuropathy progresses sharply or over weeks or months. During treatment, a reverse development occurs: the nervous system is fully or partially restored.

Subclinical symptoms

The initial stage of alcoholic polyneuropathy is detected by instrumental examination. Symptoms are not expressed. Fingers begin to feel chilly, fine motor skills and sensitivity in the arms and legs deteriorate. The disease progresses slowly unless the person goes on a binge. The first sign of development is pain in the nerve when pressing on the area where it lies.

Motor form symptoms

With this type of alcoholic polyneuropathy, motor ability is reduced. The muscles weaken, paresis or paralysis of a particular muscle group occurs. The clinic is supplemented by signs of sensory disorders (“goosebumps”, changes in sensitivity, etc.). Movements also slow down.

The knee reflex usually increases and the Achilles tendon decreases. If the fibers in the tibial nerve are damaged, they begin to walk on their toes, and plantar flexion of the foot is impaired.

Signs of damage to the peroneal nerve:

the functions of the extensor muscles deteriorate;
muscle tone and volume decrease in the foot and lower leg.

Reference! Most often, doctors identify mixed alcoholic polyneuropathy. Symptoms of the motor + sensory variety are present, nerves in the arms and legs are involved, and muscles in the extremities atrophy.

Signs of sensory form

Damage to the tissue of the peripheral nervous system is more often observed in the legs, less often in the arms. The sensations spread from the fingers up to the limbs.

For sensory alcoholic polyneuropathy:

cramps in the calf muscle become more frequent;
burning pain is felt along the area of the major nerve;
tingling and itching is felt in the limbs;
chilly hands or feet;
arms/legs become numb, muscles lose strength;
tendon reflexes, in particular the Achilles reflex, decrease;
in the palms/feet and higher up the limb, temperature and pain sensitivity increases or disappears.

Sensory impairment is often accompanied by motor and autonomic disorders. Doctors detect increased sweating. On the hands and feet, the skin color becomes marbled or bluish. Trophic ulcers form.

Signs of the pseudotabetic form

Sensitive ataxia develops. She is characterized by loss of coordination of movements and unsteady gait. When you feel the area where the nerves lie, acute pain occurs. The sensitivity of the skin in the palms, forearms or feet, legs decreases.

With alcoholic atactic polyneuropathy, there are no diabetic crises, syphilis and Argyle-Robertson syndrome. There are no “lumbago” or other signs of tabes dorsalis.

Symptoms of the vegetative form

The ganglion division of the NS regulates the reflex functions of internal organs, glands and blood vessels. Alcoholic polyneuropathy is often accompanied by disorders of the heart, circulatory and genitourinary systems.

Possible symptoms of the vegetative form:

irregular myocardial contraction;
dizziness, fainting;
drop in pressure when changing position (orthostatic hypotension);
deterioration of sexual desire;
erectile dysfunction in men;
women stop having orgasms;
urinary incontinence;
vomiting or persistent nausea;
increased sweating;
diarrhea;
flashing dots before the eyes.

Reference! Vegetative signs appear expressed or weakly in other forms of this disease. They are also similar to symptoms of progression of alcoholism.

Symptoms of alcoholic neuropathy of the lower extremities

Alcoholic polyneuropathy of the legs is accompanied by a violation of skin sensitivity: a feeling of crawling sensations, numbness. The skin of the legs becomes bluish and cool to the touch. Patients constantly feel cold in their feet. Neuropathy of the lower extremities, in which alcohol intoxication develops faster than in the arms, without treatment leads to intermittent claudication, pain when walking and at rest, and vascular inflammation. Due to the severity of the symptoms, this form of the disease is diagnosed most often.

Stages of alcoholic polyneuropathy

The disease progresses gradually. As a rule, abnormal changes in the functioning of the peripheral nervous system occur long before the first signs of the disease appear. In total, there are four stages of polyneuropathy:

Zero. The violation cannot be detected. Even a medical examination does not show that painful symptoms will soon appear. Meanwhile, optimal conditions have already been created in the alcoholic’s body to block the full activity of the peripheral nerves.
The first one. The disease proceeds secretly. There are no signs of its development, but with a comprehensive diagnosis it is possible to make a correct diagnosis. The danger of this stage is that the alcoholic feels healthy. He may think that the doctors want to scare him and refuse treatment. In this case, the disease will progress further. Dealing with it later is much more difficult.
Second. Clinical symptoms are pronounced. A neurologist can make a correct diagnosis based on the alcoholic’s complaints and diagnostic data. Significant functional impairments that interfere with a normal lifestyle are still absent or barely noticeable.
Third. Functional impairments are clearly visible. The patient cannot control his body, his ability to work is significantly reduced or completely lost.
The disease should not be started. In the early stages, it is much faster to deal with it. By delaying seeking medical help, the addict risks becoming disabled.

Diagnostics

To establish that the identified neuropathy is alcoholic, it is important to diagnose the patient’s addiction or find out about the alcohol taken before the onset of clinical manifestations. The type of toxic damage to nervous tissue must be confirmed by the results of laboratory tests. This is important because different medications are used to cleanse the body of alcohol, poison, and drugs in case of overdose. To clarify the diagnosis, they talk with the patient’s relatives about his lifestyle and the possible influence of ethanol.

Laboratory methods for diagnosing alcoholic polyneuropathy:

biochemical blood test;
biopsy of nerve and muscle tissue;
cerebrospinal fluid puncture.

Laboratory and cytohistological analysis of the biomaterial helps to detect muscle atrophy and destruction of the myelin sheath in neurons. The neurologist conducts a physical examination (examination, palpation, history taking), and refers to ENMG. Electroneuromyography can detect even asymptomatic damage to nerve fibers.

Reasons for the formation of pathology

Obvious signs of the disease make themselves felt in cases of advanced alcoholism. They are detected in patients with stages II and III of chronic alcohol dependence.

Causal factors leading to alcoholic polyneuropathy:

Toxic demyelination of neuronal axons.
Avitaminosis.
Accumulation of acetaldehydes in the blood.

Low-quality alcohol, denatured alcohols, and non-edible liquids containing ethanol have a particularly destructive effect. Sometimes one dose of a toxic substance is enough to form polyneuritis. Hereditary deficiency of enzymes that neutralize the products of ethanol catabolism in the liver is also important.

The process gets worse:
Thiamine (vitamin B1) deficiency.
Poor nutrition, due to lack of appetite during binge drinking, financial difficulties of an alcoholic who prefers to buy alcohol rather than normal food.
Violation of the detoxification function of the liver.

Treatment

Treatment of alcoholic polyneuropathy is aimed at cleansing the body of alcohol and breakdown products, regenerating neurons, restoring metabolism and blood supply to tissues. It is strictly prohibited to drink alcohol-containing drinks or medicinal tinctures.

It is important to have a balanced, nutritious diet, consume the amount of fresh fruits, vegetables, protein foods, and water. It is advisable to select the diet and food regimen according to Pevzner’s recommendations for a general diet (treatment table No. 15).

Conservative treatment includes drugs:

detoxification effect;
blood glucose regulators;
neuronal protectors, metabolisms, trophics - “Tanakan”, “Neuromidin”, others;
antioxidants – “Tiogamma”, “Berlition”, other preparations of thiocotic acid;
vasoactive drugs - “Halidor”, “Benziclan fumarate”, “Pentoxifylline”, other vasodilators, antispasmodics;
B vitamins – “Milgammacompositum”, “Berocca +”, “Benfotiamine”, others;
ascorbic acid;
antihypoxants - Actovegin.

Medicines to eliminate or reduce the symptoms of alcoholic polyneuropathy are selected individually for the patient. They use sedatives, anticonvulsants "Finlepsin", anticonvulsants "Gabapentin", antidepressants "Paroxetine". To improve brain activity, piracetam is prescribed from nootropic substances.

To relieve pain, anti-inflammatory drugs Meloxicam, Nimesulide, and antispasmodics are prescribed. In case of complications of alcoholism, medications for etiological treatment are prescribed. For liver diseases, the regimen includes hepatoprotectors of plant origin. Cardiac medications are used to support myocardial function.

The main goals of treatment for alcoholic polyneuropathy of the lower extremities are restoration of tissue trophism and prevention of the development of vascular pathologies. For this purpose, vasoactive medications are used, and detoxification therapy is mandatory. To relieve pain, NSAIDs and antispasmodics are prescribed.

Reference! Treatment of alcoholic polyneuropathy at home is impossible. Traditional methods are used only in addition to medications, exercise therapy, massage after consultation with the attending physician.

After eliminating acute intoxication, the drugs “Dibazol”, “Amiridin”, and other drugs with bendazole and ipidacrine are used. The drugs stimulate the transmission of nerve impulses, help the body adapt, increase tone, relieve muscle spasms, and dilate blood vessels. The psychologist talks with the patient about the need to give up alcohol and explains the causes of nerve damage.

During the recovery period, physiotherapy is prescribed. Massage, acupuncture, and electrical muscle stimulation are useful. These methods improve blood circulation and restore sensitivity. After treatment of alcoholic polyneuropathy of the lower extremities with drugs, physical therapy exercises are recommended. This will help restore motor functions and strengthen the body.

Forecast

With timely treatment, a reverse progression of the disease and an improvement in the patient’s quality of life are possible. A necessary condition for a favorable prognosis is a complete cessation of alcohol consumption.

According to the results of Western epidemiological studies, in the United States, alcoholic polyneuropathy is found in 25–66% of patients with chronic alcoholism.

In most cases, patients become disabled, acquiring one or another degree of disability, since early access to a specialist in this case is a rare occurrence. An important factor determining the unfavorable prognosis is the patient’s inability to give up alcohol and comply with a long-term medical and protective regime.

Prognosis for recovery

The prognosis for recovery is favorable. For recovery, it is important to undergo the necessary therapy and completely stop drinking alcohol. If you refuse treatment or continue to drink alcohol, polyneuropathy causes paralysis. The commission assigns disability group 2. Death is possible due to damage to the nerves “responsible” for breathing, heart function, and brain function. In 50% of cases, a person dies after 10 years.

Quitting alcohol, adequate treatment, daily exercise and massage allows neurons to recover. In case of disability, a transition to group 3 or full recovery is possible. Therapy followed by rehabilitation lasts at least a year.

Forms of the disease

There are acute and subacute forms of the disease.

The disease usually develops in a subacute form, progressing over many months or years. Much less common is the acute form of alcoholic polyneuropathy, which develops a few days after drinking alcohol in extreme quantities and is characterized by violent symptoms.

Alcoholic polyneuropathy is more common in women, develops in them at an earlier stage of alcoholism and is more severe than in men.

What do you need to remember?

With alcoholic polyneuropathy, neurons are damaged and the functioning of the nervous system deteriorates.
The disease develops due to the toxic effects of ethyl alcohol.
Alcoholic neuropathy of the lower extremities is the most common form of pathology.
Among the symptoms, loss of sensitivity of the skin on the extremities and movement disorders are most often observed.
Diagnosis includes electroneuromyography and laboratory tests.
Treatment and recovery of patients with alcoholic polyneuropathy of the lower extremities and other forms of pathology is possible only after complete cessation of alcohol;
Complications include disability, dysfunction of the genitourinary and cardiovascular systems.
The prognosis is favorable with timely initiation of treatment and complete abstinence from alcohol.

Literature

Vittadini G., Buonocore M., Colli G., Terzi M., Fonte R, Biscaldi G. Clinic and epidemiology of alcoholic polyneuropathy // Oxford Medical Library. Thematic collection. — Issue No. 2. — 2012. — pp. 23-29.
Vittadini G., Buonocore M., Colli G., Terzi M., Fonte R, Biscaldi G. Alcoholic polyneuropathy: clinical and epidemiological study // Oxford journals, translated licensed articles on modern medicine. Thematic collection. - 2010. - P. 6-14.
Khodulev, V.I. Electroneuromyographic characteristics of alcoholic polyneuropathy / V.I. Khodulev, N.I. Nechipurenko, S.V. Marchenko // Journal. neurol. and a psychiatrist. - 1999. - No. 12. - P. 47-49.
Anisimova, E.I. Clinical and physiological analysis of pain syndrome in polyneuropathies: Abstract of thesis. dis. ...cand. honey. Sciences / E.I. Anisimova. - M., 2002.
Acute alcoholic polyneuropathy / I.A. Strokov, V.V. Alekseev, I.V. Eisenberg, A.V. Volodina // Neurol. magazine - 2004. - T. 9. - No. 1. - P. 45-50.
Skoromets, A.A. Nervous diseases: Textbook. allowance A.A. Skoromets, A.P. Skoromets, T.A. Skoromets. — Ed. 2nd, revised and additional - M.: MEDpress-inform, 2007. - 552 p.: ill.
Alcoholism. Clinical med. / A. Adams, E.L. Goldberg, Hi Green et al. — 2 ed. St. Louis: Mosby, 1996. - P. 747-752.

Alcoholic polyneuropathy: clinical and pathogenetic variants, principles of diagnosis and treatment

Epidemiology

Alcoholism is a common and socially significant phenomenon. About 2 billion people around the world drink alcohol, and more than 76 million suffer from alcohol dependence. Chronic alcoholism is a disease characterized by the syndrome of drug addiction to alcohol. The latter leads to the development of specific somatic, neuropsychic disorders, and the emergence of social conflicts [1].

Currently, alcoholism and diseases directly related to it rank third among the causes of death, second only to cardiovascular diseases and neoplasms. According to the World Health Organization, 3.3 million people die each year worldwide as a result of alcohol consumption, accounting for 5.9% of all deaths [2]. Alcohol consumption often leads to death and disability in people of working age. In the 20–39 age group, approximately 25% of all deaths are attributable to alcohol [2].

Over the past half century, the level of alcohol consumption in Russia has increased several times. According to 2010 data presented in the report of the World Health Organization, Russia ranks fourth in the world in terms of alcohol consumption (15.1 liters per year) per capita of people aged 15 years and older [2].

Clinical picture

According to modern concepts, alcohol disease is a disease in which long-term ethanol intoxication leads to the occurrence of characteristic structural changes in the organs and systems of the body, manifested by corresponding clinical symptoms (a complex of mental, neurological and somatic disorders) [3].

The most common complication of alcoholic disease is alcoholic polyneuropathy, which occurs more often than alcoholic myopathy (diagnosed in 30–60% of patients), liver cirrhosis (15–20%), gastrointestinal tract damage (30–50%), cardiomyopathy (15 –35%), encephalopathy (1%) [4, 5]. According to various authors, the frequency of clinical forms of alcoholic polyneuropathy is 9–30%, and subclinical forms – up to 67–70% [6].

Currently, there are two main forms of alcoholic polyneuropathy: acute/subacute and chronic, which have different clinical presentations and development mechanisms, but can be combined with each other [7, 8].

Chronic alcoholic polyneuropathy

The morphological basis of damage to peripheral nerves during chronic alcohol intoxication is axonal degeneration, which is accompanied by secondary myelinopathy in the form of segmental de- and remyelination.

Chronic toxic polyneuropathy develops more often, which is caused by the direct toxic effects of ethanol and its metabolites and is accompanied by predominant damage to thin myelinated and unmyelinated fibers. The latter provide pain and temperature sensitivity and provide vegetative-trophic functions.

Clinical studies have proven that alcohol has a direct dose-dependent toxic effect on autonomic and somatic nerve fibers. An average daily dose of alcohol over 100 g significantly increases the likelihood of developing polyneuropathy, and the severity of its clinical manifestations directly depends on the total dose of ethanol [7, 8]. The mechanisms of the toxic effect of ethanol on peripheral nerves are still not well understood.

It is assumed that the toxic effect of ethanol and its metabolites on neurons occurs through activation of glutamate receptors in the spinal cord and, consequently, induction of glutamate neurotoxicity, activation of free radical lipid peroxidation, and increased production of proinflammatory cytokines. In addition, ethanol leads to a decrease in the synthesis and disruption of the normal configuration (misfolding) of nerve fiber cytoskeletal proteins and a slowdown in axonal transport [7, 9, 10]. Many representatives of the Asian race have impaired normal metabolism of ethanol due to the presence of a mutation in the gene encoding the synthesis of the enzyme aldehyde dehydrogenase. As a result, the level of toxic acetaldehyde in the body can exceed the norm by more than 20 times.

Acetaldehyde is able to form complexes with normal proteins, converting them into cytotoxic proteins, which in turn affect neurons, myocytes, and hepatocytes, leading to the development of liver cirrhosis, which further aggravates the severity of toxic alcoholic polyneuropathy. Experimental studies have obtained data on the activation of spinal cord microglial cells by ethanol and an increase in the functional activity of the hypothalamic-pituitary-adrenal and sympathoadrenal systems [11]. These changes, together with alcohol-induced oxidative stress, play a significant role in the formation of central sensitization in the spinal cord and, consequently, in the development of neuropathic pain syndrome, the phenomena of hyperesthesia and allodynia in alcoholic polyneuropathy. In general, neurons of the peripheral nervous system are more vulnerable to the effects of toxic products of alcohol metabolism than neurons of the central nervous system, protected by the blood-brain barrier.

In toxic alcoholic polyneuropathy, predominantly weakly myelinated fibers are affected, so the clinical picture is dominated by sensory and autonomic disorders. In most patients, the earliest clinical symptoms are paresthesia (sensations of “tingling”, “crawling”), as well as numbness in the distal parts of the legs; cramps in the muscles of the legs and feet are often observed. At the same time or somewhat later, a “burning” feeling and neuropathic pain in the extremities may occur, having a painful “burning”, “shooting” character, intensifying at night. It is possible to develop restless legs syndrome, the clinical basis of which is an imperative desire to move the limbs due to unpleasant sensations in them, more pronounced at night.

Toxic alcoholic polyneuropathy progresses slowly over several months or years. Beginning with damage to the distal lower extremities, symptoms spread to the proximal legs, lower torso, and in more severe cases to the upper extremities. In this clinical form, the sensory defect predominates over the motor one, and in half of the patients, even with a long course of the disease, motor disorders do not occur. Meanwhile, in other patients, weakness occurs mainly in the extensors of the feet and fingers, muscle wasting in the distal parts of the legs develops, and with a long course of the disease, weakness in the proximal parts of the legs and hands develops, and difficulty walking occurs.

A significant proportion of patients experience autonomic dysfunction, manifested by hyperhidrosis of the palms and feet, trophic disorders, changes in skin coloration, edema, as well as orthostatic hypotension, resting tachycardia, constipation, and gastroparesis. Disruption of the autonomic innervation of internal organs further aggravates metabolic disorders caused by the toxic effects of ethanol and its metabolites. Peripheral autonomic failure increases the risk of sudden death due to silent forms of myocardial infarction.

An objective neurological examination in patients most often reveals disturbances in pain and temperature sensitivity of the polyneuropathic type in the form of hypoesthesia or hyperesthesia; in some cases, symptoms of allodynia may develop. As a rule, already in the early stages of the disease, fading or loss of Achilles reflexes is noted. With further progression of the pathological process, a decrease or loss of knee reflexes, tendon reflexes from the hands, and the addition of weakness and wasting of the muscles of the extremities are revealed.

Acute and subacute alcoholic polyneuropathy

Along with chronic alcoholic polyneuropathy, characterized by slowly progressive damage to sensory, motor and autonomic fibers of peripheral nerves, there are also cases of alcoholic polyneuropathy with acute or subacute development of symptoms [6, 7, 12, 13]. In the pathogenesis of this form of alcoholic polyneuropathy, the leading role is played by deficiency of vitamin B1 (thiamine) and, possibly, other B vitamins. Alcohol consumption leads to thiamine deficiency in the body in several ways. Ethanol reduces the absorption of thiamine in the small intestine, reduces the supply of thiamine in the liver, reduces its intracellular phosphorylation, which leads to a decrease in the formation of the active form of this vitamin - thiamine diphosphate [7, 14–16]. In addition, patients suffering from chronic alcoholism, as a rule, have an inadequate, unbalanced diet, many of them develop diseases of the gastrointestinal tract (gastroduodenitis, peptic ulcer, pancreatitis), leading to malabsorption.

A decrease in the content of thiamine in the body leads to a reduction in the concentration of its active form - thiamine diphosphate, which serves as a cofactor for several enzymes involved mainly in the catabolism of carbohydrates, the biosynthesis of a number of cell constituents, components of the endogenous antioxidant system, and the synthesis of pentoses - nucleic acid precursors. As a result of vitamin B1 deficiency, the incorporation of lipids into myelin is reduced, the biosynthesis and metabolism of neurotransmitters is disrupted, and zones with lactic acidosis and intracellular calcium accumulation are formed in neurons, which potentiate the neurotoxic effect of alcohol. These data support the view that neuropathy in chronic alcohol intoxication is caused by vitamin B1 deficiency [7, 11, 16].

As a rule, the development of acute or subacute alcoholic polyneuropathy is preceded by a period of varying lengths of binge drinking, poor nutrition, and weight loss. Many patients have other manifestations of thiamine deficiency - Wernicke-Korsakoff encephalopathy, dilated cardiomyopathy. With chronic alcohol intoxication, there may be a deficiency of other B vitamins (B12, B6, B2), nicotinic and folic acids, and vitamin E. A polydeficiency state may be due to the characteristics of the clinical symptoms of polyneuropathy in each specific case, but a decrease in the content of these substances is not decisive in the development of peripheral nerve damage.

Unlike toxic polyneuropathy, thiamine-deficiency polyneuropathy usually has acute or subacute development of symptoms, although cases of slow progression are also possible. The initial symptom, as in the chronic form of alcoholic polyneuropathy, may be numbness in the distal parts of the legs, however, in most patients, due to damage to thick myelinated fibers, serious disorders of deep sensitivity develop, manifested by the syndrome of sensitive ataxia (a feeling of a “cushion” under the feet, instability and staggering when walking). walking, worse when closing eyes). Sensory disturbances are also observed in the distal parts of the arms.

Another feature of thiamine deficiency polyneuropathy is the early development and dominance of motor disorders in the clinical picture. A few days or weeks after the first symptoms of the disease, lower flaccid paraparesis debuts and increases, and then tetraparesis. Weakness of the limb muscles and sensory ataxia can be significant, limiting the ability of patients to move independently. Pain syndrome and autonomic dysfunction in this form of polyneuropathy are less common and manifest much less than in chronic toxic alcoholic polyneuropathy.

A neurological examination reveals lower paraparesis or tetraparesis with a predominance of motor disorders in the distal parts of the extremities, disorders of superficial and deep sensitivity of the polyneuropathic type, and sensitive ataxia. There is often a decrease or loss of tendon and periosteal reflexes from the lower and in some cases from the upper extremities. In some patients, cranial nerves may be involved in the pathological process, which is manifested by mild bulbar and oculomotor disorders.

Mixed form of alcoholic polyneuropathy

The most common is a mixed form of alcoholic polyneuropathy, in which the signs of toxic and thiamine-deficiency polyneuropathy are combined in various proportions and variations. Research results indicate that in the early stages of alcoholic polyneuropathy, due to the direct toxic effect of ethanol and its metabolites in the absence of nutritional deficiency and malabsorption in the intestine, the thin fibers of the leg nerves that conduct pain and temperature sensitivity suffer. With the progression of the disease and the addition of a deficiency of B vitamins, thick, well-myelinated proprioceptive and motor fibers of the peripheral nerves are involved in the pathological process [7, 8, 17].

Diagnostics

The clinical symptoms of alcoholic polyneuropathy are nonspecific, so when making a diagnosis it is important to assess the patient’s drug status and nutrition. Laboratory indicators, as a rule, reflect the degree of damage to liver tissue due to alcohol intoxication. An early sign of liver damage is considered to be elevated levels of liver transaminases (aspartate and alanine aminotransferase) or gamma-glutamyl transpeptidase. To clarify the presence of a deficiency of thiamine and other B vitamins, their concentration in the blood serum is examined. Thiamine deficiency is also confirmed by a decrease in transketolase activity of erythrocytes, which correlates with the level of thiamine in the blood. Examination of cerebrospinal fluid, as a rule, does not reveal changes [18]. Electroneuromyography is recognized as the main method for diagnosing alcoholic polyneuropathy, which makes it possible to objectify the level, nature and extent of damage to peripheral nerves. Alcoholic polyneuropathy is characterized by generalized symmetrical sensory-motor, predominantly distal axonopathy with signs of secondary myelinopathy.

When conducting stimulation electroneuromyography, a decrease in the amplitude of action potentials of sensory and motor nerves may be detected, which reflects damage to the axial cylinder of the nerve fiber - axonopathy. In addition, there is a decrease in the speed of propagation of excitation along the motor and sensory fibers of the nerves of the extremities in the distal and proximal sections, which is a sign of myelinopathy. These changes can be observed in patients who do not have clinical signs of alcoholic polyneuropathy, that is, at the subclinical stage of damage to the nerves of the extremities. As the disease progresses and neurological deficits in the sensory and motor spheres increase, the amplitudes of motor and sensory responses and the speed of propagation of excitation along the nerves decrease. In patients with acute and subacute forms of alcoholic polyneuropathy caused by thiamine deficiency, there is a more pronounced decrease in the amplitude of the motor response and the speed of excitation propagation along the motor fibers of the nerves of the limbs compared to similar indicators in toxic alcoholic polyneuropathy. These electroneuromyography results correlate with a more pronounced motor defect in patients with thiamine-deficiency polyneuropathy [7, 19–21].

In the diagnosis of various clinical forms of alcoholic polyneuropathy, needle electromyography is also used, which makes it possible to quantitatively assess the parameters of action potentials of motor units and identify signs of denervation in the muscle caused by axon damage - positive sharp waves, fibrillation potentials.

However, it should be taken into account that the absence of pathological changes according to electroneuromyography does not mean the absence of damage to peripheral nerves. The electroneuromyography method allows you to assess the condition of thick myelinated fibers of peripheral nerves. At the same time, in the chronic toxic form of alcoholic polyneuropathy, predominantly thin weakly myelinated or unmyelinated fibers are affected, so in these cases, electroneuromyography indicators remain within normal limits. To diagnose damage to thin fibers of peripheral nerves, the following techniques are used: quantitative sensory testing, laser evoked potentials, evoked potentials to thermal stimulation, and examination of intraepidermal nerve fibers.

Treatment

Considering the multifactorial mechanisms of the pathogenesis of alcoholic polyneuropathy, as well as combined damage to the liver and gastrointestinal tract, treatment in all cases requires an integrated approach under the supervision of doctors of various specialties: a neurologist, therapist, hepatologist, gastroenterologist. The prognosis for alcoholic polyneuropathy in most cases is favorable, neurological functions are restored, however, as a rule, a residual neurological defect remains. In addition, treatment requires a long period of time, since axonal regeneration and collateral sprouting are slow [7, 22].

A prerequisite for effective treatment of alcoholic polyneuropathy, as well as other manifestations of alcoholic illness, is a complete cessation of drinking alcoholic beverages, restoration of a well-balanced diet with sufficient amounts of vitamins and protein, as well as physical rehabilitation of the patient.

Many patients suffering from alcoholic polyneuropathy experience neuropathic pain syndrome. In the treatment of neuropathic pain, drugs from the group of antidepressants and anticonvulsants, as well as their combinations, are used. Among antidepressants, tricyclic antidepressants (amitriptyline), as well as serotonin and norepinephrine reuptake inhibitors (duloxetine and venlafaxine) have proven the most effective in the treatment of neuropathic pain (evidence level B). An alternative is therapy with anticonvulsants – pregabalin (evidence level A), gabapentin (evidence level B). Anticonvulsants from the valproic acid group and lamotrigine showed less effectiveness in clinical studies [7, 8, 11].

Antioxidants in the treatment of alcoholic polyneuropathy

Considering the proven role of oxidative stress in the pathogenesis of alcohol-induced peripheral nerve damage, it is reasonable to use drugs from the group of antioxidants. The most widely used in the treatment of polyneuropathy of alcoholic origin are preparations of alpha-lipoic (thioctic) acid, in particular Espa-Lipon.

Alpha lipoic acid was discovered by EE Snell et al. in 1937, who discovered that certain bacteria required potato extract to grow [23]. In 1951, LJ Reed et al. isolated the so-called potato growth factor (alpha-lipoic acid), and the participation of alpha-lipoic acid as a coenzyme in the Krebs cycle and in the elimination of free radicals was soon shown [24]. Alpha lipoic acid was originally known as an essential biochemical cofactor for mitochondrial enzymes. However, in the last decade it has been discovered that alpha lipoic acid and its metabolic intermediate dihydrolipoic acid are powerful antioxidants.

The uniqueness of alpha lipoic acid as an antioxidant lies in its ability to:

directly eliminate free radicals;
regenerate endogenous antioxidants such as glutathione, vitamins E and C;
reduce the production of free radicals due to metal chelate activity.

Alpha-lipoic acid was first used for therapeutic purposes in 1966 by German clinicians for the treatment of diabetic polyneuropathy and liver cirrhosis, as data were obtained on low levels of alpha-lipoic acid in this category of patients [25]. Alpha-lipoic acid has been shown to improve endoneurial blood flow and nerve conduction in animal models of experimental diabetes [25]. Decades of clinical use of alpha-lipoic acid have accumulated extensive evidence of its effectiveness against the symptoms of diabetic polyneuropathy.

At the same time, studies on the effectiveness of alpha-lipoic acid in alcoholic polyneuropathy are still rare. Alpha lipoic acid has been shown to be effective in 70% of patients with alcoholic polyneuropathy. It affects multimodal sensory and motor symptoms caused by damage to various peripheral nerve fibers [25]. In addition, there is evidence of a direct effect of alpha-lipoic acid on ethanol-mediated neurotoxicity in vivo [25, 26].

Treatment usually begins with intravenous administration of alpha-lipoic acid at a daily dose of 600 mg for 14–15 days. In the future, they switch to tablet forms of drugs. Espa-Lipon is recommended to be taken at a dose of 600 mg per day in the morning on an empty stomach; the duration of administration is determined by the specific clinical situation and usually varies from two to six months. In most cases, the drug is well tolerated by patients and causes virtually no side effects.

The role of B vitamins in the treatment of patients with alcoholic polyneuropathy

B vitamins, primarily B1 (thiamine), B6 (pyridoxine), B12 (cyanocobalamin), are neurotropic and have been widely used for many years in the treatment of diseases of the central and peripheral nervous system. Considering that a decrease in the concentration of thiamine (and in some cases other B vitamins) in the blood is observed in 40–80% of people with chronic alcoholism [27], and in thiamine-deficient (acute and subacute) forms of alcoholic polyneuropathy, vitamin B1 deficiency is the leading pathogenetic factor its development, the use of B vitamins in the treatment of alcoholic polyneuropathy is pathogenetically justified. Before starting treatment, it is advisable to determine the concentration of thiamine in the blood or evaluate the activity of erythrocyte transketolase [7, 27]. B vitamins can be prescribed in the absence of their deficiency due to the active participation of this group of vitamins in biochemical processes that ensure the normal functioning of the structures of the nervous system [28].

In practice, in the treatment of alcoholic polyneuropathy, combination preparations of B vitamins are most often used. In addition to thiamine, they include pyridoxine (vitamin B6) and cyanocobalamin (vitamin B12). Experimental and clinical studies have shown that the components of combination preparations of B vitamins potentiate each other’s effects [27].

The active form of thiamine, thiamine diphosphate, is necessary for the oxidative decarboxylation of keto acids (pyruvic and lactic) and the synthesis of acetylcholine. Acetylcholine is involved in carbohydrate metabolism and ensuring axonal transport, which determines the regeneration of nervous tissue, and also has a regulatory effect on the trophism of the nervous system. Thiamine in alcoholic neuropathy, replenishing the resulting deficiency and restoring the activity of key enzymes, allows you to stop the progression of polyneuropathy and promotes a more complete and rapid recovery of the neurological deficit.

The phosphorylated form of pyridoxine serves as a cofactor for more than 100 enzymes and takes part in the synthesis of various mediators: catecholamines, histamine and gamma-aminobutyric acid. In its phosphorylated form, the drug ensures the processes of decarboxylation, transamination, deamination of amino acids, participates in the synthesis of protein, enzymes, hemoglobin, prostaglandins, improves the absorption of unsaturated fatty acids, reduces the level of cholesterol and lipids in the blood, improves myocardial contractility, promotes the conversion of folic acid into its active form . In addition, it increases intracellular reserves of magnesium, which plays an important role in metabolic, in particular energy, processes in the nervous system.

Vitamin B12 is involved in the construction of protein and fatty structures of the myelin sheath of nerve fibers; as part of coenzymes, it promotes cell replication and growth. Vitamin B12 and methionine (as well as vitamin C) play an important role in the functioning of the central and peripheral nervous system, participating in metabolism in the production of monoamines [27–29].

Controlled studies have proven the effectiveness of B complex vitamins in the treatment of positive and negative symptoms of alcoholic polyneuropathy [28]. It should be noted that the studies included patients who had a sensory form of polyneuropathy. It can be assumed that the main cause of peripheral nerve damage was the toxic effect of ethanol, and not thiamine deficiency. The obtained therapeutic effect confirms the advisability of prescribing B vitamins to patients with chronic alcohol intoxication in the presence of polyneuropathy, regardless of its pathogenetic mechanisms (toxic or thiamine deficiency). Considering that deficiency of B vitamins plays a leading role in the development of other clinical forms of damage to the nervous system in alcoholism (Haye-Wernicke-Korsakoff encephalopathy, alcoholic dementia), it is advisable to prescribe them in these cases as well.

The use of the water-soluble form of thiamine orally in therapeutic doses is limited by its relatively low bioavailability: water-soluble thiamine is poorly absorbed and is partially destroyed by intestinal thiaminase, in which it is mainly absorbed. When increasing the dose of water-soluble thiamine, a “saturation” effect occurs when, despite increasing the dose, its concentration in the blood does not increase significantly, which is explained by blocking its transfer from the intestine to the blood. After the concentration of thiamine in the blood increases to more than 2 µmol/l, active sodium-dependent transport is replaced by less effective passive diffusion. The maximum possible absorption from the gastrointestinal tract is 10%, and no more than 15 mg can be absorbed per day. At high concentrations in the blood, thiamine is actively excreted by the kidneys almost unchanged.

The solution to this problem was the creation of fat-soluble forms of thiamine that do not have the disadvantages inherent in the water-soluble oral form of vitamin B1. Such forms were synthesized in Japan in the 1950s. to prevent pandemic beriberi disease, and the entire group of fat-soluble thiamines was named allithiamins. Benfotiamine among all allithiamins has the greatest bioavailability and the least toxicity, penetrating into the body through the mechanism of passive dose-dependent diffusion, it has almost 100% bioavailability. In addition, benfotiamine is not destroyed by intestinal thiaminases, which makes it possible to achieve maximum effect when using it. It has been established that benfotiamine increases the activity of the transketolase enzyme [27, 28, 30, 31].

The controlled BAP 1 STUDY study demonstrated the effectiveness of benfotiamine against sensory and motor manifestations of alcoholic polyneuropathy [30, 31].

In addition, in the middle of the twentieth century. the analgesic effect of B vitamins has been established. It is believed that vitamin B12 has the most pronounced analgesic properties. According to the results of modern studies, benfotiamine also significantly reduces the intensity of pain in alcoholic polyneuropathy [32].

Experimental work has shown that under the influence of a combination of B vitamins, nociceptive responses caused by formaldehyde are inhibited, which is not observed after the administration of naloxone. It is believed that the antinociceptive effect of the combined vitamin complex may be due to inhibition of synthesis and/or blocking the action of inflammatory mediators.

It has been established that the B complex of vitamins enhances the effect of the main antinociceptive neurotransmitters - norepinephrine and serotonin. In addition, animal experiments revealed suppression of nociceptive responses not only in the dorsal horn of the spinal cord, but also in the thalamus optica.

Clinically and in experimental models, B vitamins have been shown to enhance the analgesic effect of nonsteroidal anti-inflammatory drugs, anticonvulsants, and antidepressants in neuropathic pain syndromes. Given the significant prevalence of neuropathic pain in patients with alcoholic polyneuropathy, the analgesic effect of vitamin B complex is of important therapeutic importance.

Dosage forms and routes of administration of B vitamins

Monotherapy with vitamins B1, B6 or B12 can be carried out. There are water-soluble forms for parenteral administration and for oral administration in the form of tablets or dragees. To quickly achieve high concentrations of vitamins in the blood and cytoplasm of cells, preference is given to parenteral administration of large doses of water-soluble forms of B vitamins.

However, in case of alcoholic polyneuropathy, it is advisable to use B vitamins not alone, but in combination. A widely known combination preparation of B vitamins is Milgamma (ampoules), which contains 100 mg of thiamine, 100 mg of pyridoxine and 1000 mcg of cyanocobalamin. Considering that thiamine deficiency in alcoholic polyneuropathy in many cases develops due to impaired absorption in the intestine, it is advisable to begin treatment of severe forms of alcoholic polyneuropathy with parenteral administration of the drug. This ensures a faster and more guaranteed onset of the therapeutic effect. Milgamma is usually prescribed intramuscularly in a dose of 2 ml (one ampoule) for ten days. Milgamma has a small ampoule volume (only 2 ml), and also contains the local anesthetic lidocaine (20 mg), which makes injections virtually painless and increases patient adherence to therapy [28].

After parenteral administration, it is necessary to consolidate the effect by oral administration of B vitamins, for which you can use the drug Milgamma compositum, containing 100 mg of lipophilic benfotiamine and 100 mg of pyridoxine. The standard treatment course involves taking three tablets per day for two to three months.

In all cases, patients with alcoholic polyneuropathy require continuous long-term administration of thiamine. When prescribing combination drugs, it should be taken into account that with long-term use of high doses of pyridoxine, there is a risk of developing toxic sensory polyneuropathy [27, 28]. For long-term maintenance therapy of alcoholic polyneuropathy, the drug Benfogamma is especially suitable, which contains 150 mg of benfotiamine and is taken one tablet per day for a long time.

Thus, the results of controlled clinical studies have proven the pathogenetic validity, effectiveness and safety of the use of combined preparations of B vitamins for alcoholic polyneuropathy.

Characteristic

Polyneuropathy is multiple damage to peripheral nerves of various etiologies; there are vitamin deficiency (lack of B vitamins), inflammatory demyelinating, diabetic, and alcoholic toxic forms. The pathology is manifested by sensitivity disorders, flaccid paralysis, impaired trophism (nutrition) of tissues, vegetative-vascular disorders affecting mainly distal (remote from the center of the body) segments of the limbs.

Alcoholic polyneuropathy is a disease that develops against the background of abuse of alcohol-containing drinks, which plays a leading role in the pathogenesis of the toxic effects of ethanol on the tissues of the central nervous system. Clinical studies show that polyneuropathy due to alcohol abuse occurs with a daily dose of ethanol of 100 ml (with interruptions). Pathology is detected in the majority of patients suffering from alcoholism. In ICD-10, alcoholic polyneuropathy is listed under the code “G62.1”.