Neuropathy of the legs: diabetic, alcoholic, peripheral, sensory, toxic

Any neurological foot disease, defined as the neuropathy of the lower limbs, is associated with damage to the nerves that provide motor and sensory innervation of their muscles and skin. This can lead to a weakening or total loss of sensitivity, as well as the loss of the ability of muscle fibers to strain and come into tonus, that is, locomotion of the musculoskeletal system.

[1], [2], [3], [4], [5], [6], [7], [8]

Epidemiology

In patients with diabetes, the incidence of lower extremity neuropathy exceeds 60%. And CDC statistics indicate the presence of peripheral neuropathy in 41.5 million Americans, that is, almost 14% of the US population. Such figures may seem unrealistic, but the National Institute of Diabetes specialists note that about half of the patients do not even know that they have this pathology, because the development of the disease is at an early stage, and they do not even complain about some discomfort from numbness of the toes the doctor.

According to experts, peripheral neuropathy is detected in 20-50% of HIV-infected patients and in more than 30% of cancer patients after chemotherapy.

Hereditary neuropathy of Charcot-Marie-Toot affects 2.8 million people worldwide, and the frequency of Guillain-Barre syndrome is 40 times less, as is the diagnosed multiple myeloma.

The frequency of cases of alcoholic neuropathy (sensory and motor) varies from 10% to 50% of alcoholics. But, if electrodiagnostic methods are used, neurological problems with the legs can be detected in 90% of patients with prolonged alcohol dependence.

[9], [10], [11], [12], [13],

Causes of the neuropathy of the lower extremities

In modern neurology, the most common causes of neuropathy of the lower limbs are:

• injuries in which broken bones or their dense gypsum fixation (longettes, tires) can exert pressure directly on the motor nerves;
• stenosis (constriction) of the spinal canal in which the spinal cord nerve is located, as well as the compression of its ventral branches or the inflammation of individual nerve roots;
• craniocerebral trauma, stroke, brain tumors (primarily in the zones of extrapyramidal system, cerebellum and subcortical motor nuclei);
• infection, including Varicella zoster-induced herpetic myelitis,  Guillain-Barré syndrome  (developing with lesions of the herpesvirus type IV of the subfamily Gammaherpesvirinae), diphtheria, hepatitis C,  Lyme disease  (tick-borne borreliosis), AIDS, leprosy (caused by the Mycobacterium leprae bacterium), meningoencephalitis of various etiology;
• metabolic and endocrine diseases - diabetes mellitus of both types, porphyria, amyloidosis, hypothyroidism (a deficiency of thyroid hormones), acromegaly (excess of growth hormone);
• autoimmune diseases: rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis (with destruction of the myelin of the nerve shells), acute disseminated encephalomyelitis;
• hereditary diseases: Charcot-Marie-Toot neuropathy, Friedreich's neurodegenerative ataxia, hereditary sphingolipidosis or  Fabry's disease; glycogenesis of the second type (Pompe disease, caused by a defect in the gene of the lysosomal enzyme maltase);
• disease of motor (motor) neurons - amyotrophic lateral sclerosis;
• subcortical atherosclerotic encephalopathy with atrophic change in white matter of the brain (Binswanger's disease);
• multiple myeloma  or multiplexed plasma-cell myeloma (in which malignant degeneration affects plasma B lymphocytes);
• Lambert-Eaton syndrome (noted for small cell lung cancer), neuroblastoma. In such cases, neuropathies are called paraneoplastic;
• systemic vasculitis (inflammation of the blood vessels), which can provoke the development of nodular periarthritis with violation of the innervation of the lower limbs;
• radiation and chemotherapy of malignant neoplasms;
• toxic effects of ethyl alcohol, dioxin, trichlorethylene, acrylamide, herbicides and insecticides, arsenic and mercury, heavy metals (lead, thallium, etc.);
• side effects of some long-acting drugs, such as anti-tuberculosis drugs isonicotinic acid, anticonvulsant drugs of the hydantoin group, fluoroquinolone antibiotics, lipid-lowering statins, as well as an overdose of pyridoxine (vitamin B6);
• insufficient level of cyanobobalamin and folic acid (vitamins B9 and B12) in the body, leading to the development of funicular myelosis.

[14], [15]

Risk factors

Physicians unanimously attribute the weakening of immunity, which affects the resistance of the organism to bacterial and viral infections, and also heredity (the family history of the disease) to the risk factors for neuropathy of the lower limbs.

In addition, the development of diabetes affects obesity and metabolic syndrome, poor kidney and liver function; multiple sclerosis - diabetes, intestinal problems and thyroid pathologies.

The risk factors for systemic vasculitis are HIV, hepatitis and herpes viruses, increased sensitization of the organism of various etiologies. And the plasma cell myeloma develops more easily in those who have excess weight or alcohol dependence.

In most cases, the lack of blood supply to the brain causes necrosis of its tissues, but when the myelin sheath of nerve fibers does not receive oxygen, it gradually degenerates. And this condition can be observed in patients with cerebrovascular disease.

In principle, all of the above diseases can be attributed to factors that increase the likelihood of a neurological disorder of motor functions.

[16], [17], [18]

Pathogenesis

The pathogenesis of neurological problems with legs depends on the causes of their occurrence. Physical trauma can be accompanied by the compression of nerve fibers, exceeding their ability to stretch, because of which their integrity is violated.

The pathological effect of glucose on the nervous system has not yet been elucidated, however, with a prolonged excess of blood glucose, the violation of the conduction of nerve signals along the motor nerves is an indisputable fact. And with insulin-dependent diabetes, not only the violation of carbohydrate metabolism, but also the functional insufficiency of many endocrine glands, affecting the overall metabolism.

The pathophysiological component of neuropathy in Lyme disease has two versions: Borrelia bacteria can provoke an immune-mediated attack on the nerve or directly damage its cells with its toxins.

With the development of amyotrophic lateral sclerosis, the main pathogenetic role is played by replacement of the dead motor neurons of the corresponding brain structures with nodes of glial cells that do not perceive nerve impulses.

In the pathogenesis of demyelinating neuropathies (including the most common is hereditary peroneal amyotrophy or Charcot-Marie-Toot disease), genetic defects in the synthesis of Schwann cells cells of nerve fibers - myelin, 75% lipid and 25% protein of neuregulin. Spreading the nerve along its entire length (with the exception of the small unmyelinated Ranvier nodes), the myelin sheath protects the nerve cells. Without it - due to degenerative changes in axons - the transmission of nerve signals is disrupted or completely discontinued. In the case of Charcot-Marie-Toot disease (with a lesion of the peroneal nerve that transmits impulses to the peroneal muscles of the lower extremities extending the foot), mutations are noted on the short arm of chromosome 17 (PMP22 and MFN2 genes).

Multiple myeloma affects B-lymphocytes emerging from the embryonic center of the lymph node, disrupting their proliferation. And this is the result of chromosomal translocation between the immunoglobulin heavy chain gene (in 50% of cases - on chromosome 14, at the locus q32) and oncogene (11q13, 4p16.3, 6p21). The mutation leads to oncogene dysregulation, and the growing tumor clone produces an abnormal immunoglobulin (paraprotein). And produced antibodies lead to the development of amyloidosis of peripheral nerves and polyneuropathy in the form of paraplegia of the legs.

The mechanism of poisoning with arsenic, lead, mercury, tricresyl phosphate consists in increasing the content of pyruvic acid in the blood, breaking the balance of thiamine (vitamin B1) and decreasing the activity of cholinesterase (an enzyme that provides synaptic transmission of nerve signals). Toxins provoke the initial decomposition of myelin, which triggers autoimmune reactions, which manifest themselves in the swelling of myelinated fibers and glial cells with their subsequent destruction.

With alcoholic neuropathy of the lower extremities under the action of acetaldehyde, there is a decrease in intestinal absorption of vitamin B1 and a reduction in the level of thiamine pyrophosphate coenzyme, which leads to disruption of many metabolic processes. So, the level of lactic, pyruvic and d-ketoglutaric acids rises; the absorption of glucose deteriorates and the level of ATP necessary for maintaining neurons decreases. In addition, studies have revealed in alcoholics damage to the nervous system at the level of segmental demyelination of axons and loss of myelin at the distal ends of long nerves. The metabolic effects of liver damage associated with alcoholism, in particular, the deficiency of lipoic acid, play a certain role.

[19], [20], [21]

Symptoms of the neuropathy of the lower extremities

Typical clinical signs of neuropathy of the lower extremities are related to the type of the affected nerve.

If the sensory nerve is damaged, the first signs are manifested by tingling and a feeling of "crawling" in the skin, and these are symptoms of paresthesia (numbness).

In addition, there may be: a burning sensation of the skin and an increase in its sensitivity (hyperesthesia); inability to feel temperature changes and pain or, conversely, hypertrophied pain sensations (hyperalgesia, hyperpathy, or allodynia); loss of coordination of movements (ataxia) and orientation of limb position (proprioception).

Motor neuropathy affects the muscles and manifests itself:

• twitching of muscles and cramps;
• periodic involuntary contractions of individual muscle fibers (fasciculations);
• weakening or lack of reflexes of the biceps femoris, knee and Achilles tendons;
• weakness and atrophy of the leg muscles, leading to instability and difficulty in moving;
• flaccid one-sided or bilateral partial paralysis (paresis);
• one-sided hemiplegia or bilateral full paralysis of the legs (paraplegia).

Symptoms of ischemic neuropathy include: acute pain, swelling, skin hyperemia, lack of sensitivity on the back of the foot, and then in the proximal limb.

Symptoms can develop rapidly (as with Guillain-Barre syndrome) or slowly for several weeks and months. Symptoms usually occur in both legs and begin with the fingertips.

Forms

Among the neurological disorders, the following types of neuropathy of the lower extremities are distinguished.

Motor neuropathy of the lower limbs, that is, motor, develops because of the disturbance of the conductive function of the efferent nerves that transmit signals from the central nervous system to the peripheral and that provide muscle contraction and movement of the legs.

Sensory neuropathy of the  lower limbs arises when damaged

Afferent (sensory) fibers distributed over many peripheral nerves, and their receptors (related to the peripheral nervous system) are found in the skin and soft tissues, providing mechanoreception (tactile sensations), thermoreception (sensations of heat and cold) and nociception (pain sensitivity)

Sensory motor neuropathy of the lower limbs is a simultaneous disruption of the conduction of motor nerves and sensory fibers, and since the peripheral nervous system is affected, there is a definition - peripheral neuropathy of the lower limbs. It can affect only one nerve (mononeuropathy) or several nerves simultaneously (polyneuropathy). When two or more separate nerves are affected in disparate areas of the body, this is a multifocal (multiple) neuropathy.

Neurological syndromes can be a complication of type 1 and type 2 diabetes, and in clinical neurology, diabetic neuropathy of the lower limbs is diagnosed (often sensory, but may be sensory and sensorimotor).

The most common type of progressive loss of sensory function of individual nerves in patients with diabetes mellitus is the distal sensory neuropathy of the lower limbs, that is, affecting the remotest parts of the nerve - with symmetrical numbness (paresthesia) of the feet. With proximal neuropathy, the absence of mechano and thermoreception is noted in the legs, thighs and gluteus muscles.

Traumatic or ischemic neuropathy of the lower limbs, as a rule, is diagnosed in cases of fractures of the bones - femoral and tibial, and is caused by compression of nerve fibers and caudal branches of the motor nerves, blood flow disturbance and damage to the muscles of the lower extremities.

Alcoholic neuropathy of the lower extremities is revealed when the pathology is associated with alcohol abuse.

Toxic neuropathy of the lower limbs is the result of the neurotoxic effect of a number of substances (which were listed above).

[22], [23], [24], [25]

Complications and consequences

Neurological pathologies of the lower limbs can have negative consequences and complications, in particular:

• burns and skin trauma due to loss of sensory nerve function;
• infectious soft tissue lesions (in patients with diabetes);
• weakness of the foot muscles and loss of coordination can lead to an unbalanced pressure exerted on the ankle during walking, causing it to deform with time.

Peripheral neuropathy affects the motor nerves, and the consequence may be partial or complete inability of muscle fibers to strain and come into tone - in order to provide the functions of the musculoskeletal system.

[26], [27]

Diagnostics of the neuropathy of the lower extremities

Complex diagnosis of lower extremity neuropathy suggests:

• physical examination (with testing of tendon reflexes), detailed history and detailed analysis of symptoms;
• laboratory tests - blood tests (general and biochemical, for sugar and glucagon, for antibodies, for the maintenance of various enzymes, thyreotropic and some other hormones); blood and urine tests for paraprotein.

Instrumental diagnostics includes: electromyography (determination of electrical activity of muscles), electroneuromyography (investigation of nerve conduction), x-ray of the spine, contrast myelography, CT of spinal cord and MRI of the brain, ultrasonic angiography of cerebral vessels.

[28], [29], [30]

Differential diagnosis

On the basis of symptoms, standard laboratory and additional examinations (biopsies of nerves and muscles, as well as biopsy - for the study of peripheral nerves) differential diagnostics is carried out.

Treatment of the neuropathy of the lower extremities

Treatment, aimed at the main cause of neuropathy, can prevent further damage to the nerves, but it is not always possible. Then prescribe therapy symptomatic, and also use methods of maintaining muscle tone and physical functions of the lower extremities.

For example, in cases of bacterial infection, such as leprosy or Lyme disease, antibiotics are used.

Neuropathy of the lower limbs, caused by diabetes, can be treated by monitoring blood sugar levels, including with the use of preparations of thioctic acid (Tyoktatsida, Oktolipen, Tiogamma, etc.). These drugs are also used for alcohol and toxic neuropathies. Read more -  Treatment of diabetic neuropathy

When pathology occurs due to a lack of vitamins, intramuscularly injected with vitamins B1 and B12, and inside take vitamins A, E, D, as well as calcium and magnesium.

With peripheral neuropathy that accompanies autoimmune diseases, plasmapheresis and intravenous corticosteroids and immunoglobulins are administered with multiple motor neuropathy, as well as in the initial stage of Guillain-Barr syndrome.

Human immunoglobulin with IgG antibodies (available under the trade names Intraglobin, Pentaglobin, Sandoglobin, Cytopekt, Imbiogam, etc.) is administered iv / drip (the dose is determined on an individual basis). Preparations of this group are contraindicated in the presence of kidney failure, severe allergy and diabetes. The side effects of immunoglobulins can be manifested by chills, fever, headache, general weakness and increased drowsiness; it is not ruled out that the allergic reaction with cough and spasm of the bronchi, as well as nausea and vomiting.

If patients do not suffer from bronchial asthma, angina or epilepsy, the use of drugs of the group of reversible inhibitors of cholinesterase is indicated: Oxazil, Amiridin, Neuromidine, Galanthamine hydrobromide, etc. Thus, Oxazil is ingested (0.01 g three times a day), and 1% Galantamine solution is administered subcutaneously - once or twice a day.

Anesthetics are used for neuropathy of the lower extremities: tricyclic antidepressants (Nortriptyline), non-steroidal anti-inflammatory drugs (Naproxen, Ketoprofen, Meloxicam or Ibuprofen - one tablet once a day).

Locally from pain, ointments and gels are used for neuropathy of the lower extremities: Ketonal (Fastum gel, Bystrumgel) with ketoprofen; Diclofenac (Diclac, Diclofen, Voltaren emulgel); Nase gel (with nimesulide). Also, doctors advise ointments with bitter pepper extract capsaicin (Capsicum, Espol, Finalang), which not only relieve pain, but also improve trophic tissue.

In cases of nerve damage due to squeezing or swelling, surgical treatment is used.

Practically in all cases, medicamentous therapy is complemented by physiotherapy treatment of lower extremity neuropathy: electrophoresis, acupuncture, magnetotherapy, ozone therapy, therapeutic massage, balneological procedures. To maintain muscle tone and work of the musculoskeletal system is assisted by exercise therapy and exercises with neuropathy of the lower limbs.

In addition, daily gymnastics with neuropathy of the lower limbs or a walk for an hour help control blood sugar levels and stimulate blood circulation.

Alternative treatment

Some patients can alleviate the manifestations of peripheral neuropathy alternative treatment:

• intake of evening primrose oil containing alpha-lipoic and gamma-linolenic fatty acids;
• daily intake of 4 grams of fish oil (a source of omega-3 fatty acids) or a tablespoon of flaxseed oil;
• extract of grape seeds (from demyelination of nerves);
• extract of fungus Ericeusa geritsievogo (Hericium erinaceus), which contributes to the normal formation of myelin sheaths of nerve fibers;
• foot massage with castor oil (every other day).

And the recommended treatment with herbs includes the reception of broths and infusions of St. John's wort, elecampane, blueberry or blueberry leaf, Coleus forskohlii and scotchia (Cotini coggygriae), as well as Amla extract or Indian gooseberry (Emblica officinalis).

[31], [32], [33], [34], [35]

Nutrition for lower extremity neuropathy

A special diet for neuropathy of the lower extremities is not prescribed by neurologists, but recommendations for proper nutrition must be taken into account.

For example, you need to eat foods rich in fatty omega-acids: fresh fish (mackerel, tuna, salmon, herring, sardines, trout), nuts, peanuts, olive oil.

By the way, fish, as well as meat by-products replenish the stocks of vitamin B12, and legumes, rice, buckwheat, oatmeal, garlic, sunflower seeds and pumpkin - vitamin B1.

To saturate the body with L-carnitine, the diet should include red meat and dairy products (primarily cheese and cottage cheese).

Prevention

In the prevention of diabetic neuropathy included diet (to significantly reduce the amount of carbohydrates) and increase physical activity - morning exercise.

Peripheral neuropathies can be prevented only if it is possible to avoid the diseases that lead to them. Steps that a person can take to prevent potential problems include vaccines against diseases that cause neuropathy, such as poliomyelitis and diphtheria.

Precautions when using certain chemicals and drugs are recommended to prevent neurotoxic effects. A control of chronic diseases, such as diabetes, can also reduce the chances of developing peripheral neuropathy.

[36], [37], [38], [39], [40], [41]

Forecast

The prognosis of the development and outcome of neuropathy of the lower extremities varies depending on the underlying cause and damage to the nerves - from a reversible problem to a potentially fatal complication. In mild cases, the damaged nerve is regenerated. Dead nerve cells can not be replaced, but after damage they are able to recover. And with congenital demyelinating neuropathies, complete recovery is impossible.

Assess the prospects of patients with alcohol neuropathy is difficult, because it is difficult to persuade chronic alcoholics to stop drinking alcohol. Although their neurological problems with their legs can lead to severe disability.

[42], [43], [44],