Overview of Demyelinating Disorders – Brain, Spinal Cord, and Nerve Disorders

By

Michael C. Levin

, MD, College of Medicine, University of Saskatchewan

Reviewed/Revised May 2023

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Most nerve fibers inside and outside the brain are wrapped with many layers of tissue composed of a fat (lipoprotein) called myelin. These layers form the myelin sheath. Much like the insulation around an electrical wire, the myelin sheath enables nerve signals (electrical impulses) to be conducted along the nerve fiber with speed and accuracy. When the myelin sheath is damaged, nerves do not conduct electrical impulses normally. Sometimes the nerve fibers are also damaged.

If the sheath is able to repair and regenerate itself, normal nerve function may return. However, if the sheath is severely damaged, the underlying nerve fiber can die. Nerve fibers in the central nervous system (brain and spinal cord) cannot fully regenerate themselves. Thus, these nerve cells are permanently damaged.

Insulating a Nerve Fiber

Some disorders that cause demyelination affect mainly the central nervous system. Others, such as chronic inflammatory demyelinating polyneuropathy Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Chronic inflammatory demyelinating polyneuropathy is a form of polyneuropathy that, like Guillain-Barré syndrome, causes increasing muscle weakness, but the weakness progresses for more than. .. read more , affect mainly nerves in other parts of the body.

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When babies are born, many of their nerves lack mature myelin sheaths. As a result, their movements are jerky, uncoordinated, and awkward. As myelin sheaths develop, movements become smoother, more purposeful, and more coordinated.

Myelin sheaths do not develop normally in children with certain rare hereditary diseases, such as Tay-Sachs disease Tay-Sachs Disease and Sandhoff Disease Tay-Sachs disease and Sandhoff disease are types of lysosomal storage disorder called sphingolipidoses and are caused by a buildup of gangliosides in the tissues in the brain. These diseases… read more , Niemann-Pick disease Niemann-Pick Disease Niemann-Pick disease is type of lysosomal storage disorder. Types A and B are sphingolipidoses and are caused by a buildup of sphingomyelin in the tissues. Type C is a lipidosis that is caused… read more , Gaucher disease Gaucher Disease Gaucher disease is a type of lysosomal storage disorder called a sphingolipidosis. It is caused by a buildup of glucocerebrosides in tissues. Children who have the infantile form usually die… read more , and Hurler syndrome. Children with such disorders may have permanent, often extensive, neurologic problems.

In adults, the myelin sheath can be damaged or destroyed by the following:

• Stroke Overview of Stroke A stroke occurs when an artery to the brain becomes blocked or ruptures, resulting in death of an area of brain tissue due to loss of its blood supply (cerebral infarction) and symptoms that… read more

• Infections

• Immune disorders

• Metabolic disorders

• Nutritional deficiencies (such as a lack of vitamin B12 Vitamin B12 Deficiency Vitamin B12 deficiency can occur in vegans who do not take supplements or as a result of an absorption disorder. Anemia develops, causing paleness, weakness, fatigue, and, if severe, shortness… read more )

• Poisons (such as carbon monoxide Carbon Monoxide Poisoning Carbon monoxide is a colorless, odorless gas that is produced when many materials are burned and can be toxic when breathed in large amounts Carbon monoxide poisoning is common. Symptoms may… read more )

• Drugs or medications (such as the antibiotic ethambutol)

• Excessive use of alcohol Alcohol Use Alcohol (ethanol) is a depressant (it slows down brain and nervous system functioning). Consuming large amounts rapidly or regularly can cause health problems, including organ damage, coma,… read more

Destruction of the myelin sheath is called demyelination.

Some disorders that cause demyelination have no known cause. These disorders are called primary demyelinating disorders. The most common of these disorders is

• Multiple sclerosis Multiple Sclerosis (MS) In multiple sclerosis, patches of myelin (the substance that covers most nerve fibers) and underlying nerve fibers in the brain, optic nerves, and spinal cord are damaged or destroyed. The cause… read more

Other primary demyelinating disorders include

• Acute disseminated encephalomyelitis Acute Disseminated Encephalomyelitis (ADEM) Disorders that cause demyelination and have no known cause are called primary demyelinating disorders. Demyelination is the destruction of the tissues that wrap around nerves, called the myelin… read more

• Adrenoleukodystrophy and adrenomyeloneuropathy Adrenoleukodystrophy and Adrenomyeloneuropathy Disorders that cause demyelination and have no known cause are called primary demyelinating disorders. Demyelination is the destruction of the tissues that wrap around nerves, called the myelin… read more

• Leber hereditary optic neuropathy Leber Hereditary Optic Neuropathy Disorders that cause demyelination and have no known cause are called primary demyelinating disorders. Demyelination is the destruction of the tissues that wrap around nerves, called the myelin… read more

• Neuromyelitis optica spectrum disorder Neuromyelitis Optica Spectrum Disorder (NMOSD) Neuromyelitis optica spectrum disorder affects mainly the nerves in the eyes and spinal cord, causing patches of myelin (the substance that covers most nerve fibers) and the nerve fibers under. .. read more (neuromyelitis optica)

Sometimes primary demyelinating disorders develop after a viral infection or vaccination against a viral infection. A likely explanation is that the virus or another substance somehow triggers the immune system to attack the body’s own tissues (autoimmune reaction Autoimmune Disorders An autoimmune disorder is a malfunction of the body’s immune system that causes the body to attack its own tissues. What triggers an autoimmune disorder is not known. Symptoms vary depending… read more ). The autoimmune reaction results in inflammation, which damages the myelin sheath and the nerve fiber under it.

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Types, Causes, Symptoms, and Treatments

Myelin is an insulating layer of lipids and proteins surrounding nerves. Myelin damage can cause problems with the nerves’ ability to send and receive electrical messages. Inflammatory disorders often cause myelin damage, but there are other causes.

When you think of myelin, imagine the insulation around an electrical wire.

Damage to myelin can make it harder for you to move around, perform ordinary tasks, and even see what you’re doing sometimes. Fatigue is also common.

Inflammation is one common cause of damage to myelin, but other things can cause demyelination, including:

• viral infections
• loss of oxygen
• physical compression
• metabolic problems

Discover what disorders that can develop when your nerves experience damage to the myelin sheath around them.

There are two main categories of demyelinating disease: demyelinating disease of the central nervous system (CNS) and demyelinating disease of the peripheral nervous system (PNS).

CNS demyelinating disease

This category of disease includes conditions such as:

• Multiple sclerosis (MS): MS is the most common type of demyelinating disease of the central nervous system, and affects about 1 million people in the United States.
• Optic neuritis: Optic neuritis is inflammation of the optic nerves. It affects about half of all people with MS.
• Transverse myelitis: Transverse myelitis is inflammation of both sides of a section of the spinal cord. About 1,400 new cases are diagnosed each year in the United States, with about 33,000 people experiencing symptoms or disability as a result of this condition.
• Acute disseminated encephalomyelitis (ADEM): ADEM is a severe bout of inflammation in which swelling damages the myelin on cells in the brain, spinal cord, and sometimes the optic nerves.
• Neuromyelitis optica (NMO): Neuromyelitis optica affects the eyes and the spinal cord first, and eventually also may affect the brain. Also known as Devic’s disease, it’s a rare disease that affects only about 4,000 people in the United States.
• Adrenoleukodystrophy: There are three different kinds of adrenoleukodystrophy: childhood cerebral ALD, adrenomyelopathy, and Addison’s disease. It affects about 1 in every 20,000 to 50,000 people.

PNS demyelinating disease

This category includes conditions such as:

• Chronic inflammatory demyelinating polyneuropathy: Also known as chronic relapsing polyneuropathy, CIDP causes progressive muscle weakness and affects roughly 5 to 7 out of every 100,000 people.
• Guillain Barré-syndrome (GBS): GBS is an autoimmune disorder in which your immune system attacks the cells of your peripheral nervous system. It’s considered rare, as it affects only about 1 in 100,000 people in the United States.

In many of these disorders, the exact cause isn’t known. Scientists are learning more about them, as research is ongoing, but here’s what they know now:

Condition	Cause
Multiple sclerosis	The exact cause is still unknown, although experts believe that genetic and environmental factors may be at work. Women are two to three times more likely to develop MS.
Optic neuritis	You are at increased risk for developing optic neuritis if you already have MS or NMO. Infections and other diseases sometimes give rise to inflammation of the optic nerve, too. But the exact cause is not yet completely understood.
Transverse myelitis	Experts speculate that it could be immune-mediated, or it could be the result of an infection. It sometimes develops as an early symptom of MS. But it’s estimated that in 16-60 percent of cases, the exact cause isn’t known.
Acute disseminated encephalomyelitis	Again, while scientists still hope to pinpoint an exact cause, the general thinking is that a viral or bacterial infection may cause the inflammation that’s the hallmark of this condition. It tends to affect more children than adults.
Neuromyelitis optica	It often strikes in childhood, but it can also affect adults and is more common in women than in men. In fact, more than 80 percent of diagnosed cases of NMO occur in women.
Adrenoleukodystrophy	This disorder affects the nervous system and the adrenal glands. It’s an X-linked recessive inherited condition, which means that it’s caused by a mutation on a gene on the X chromosome. So it tends to affect more men than women.
Chronic inflammatory demyelinating polyneuropathy	Some experts suspect that this may be a chronic version of a common form of Guillain-Barré syndrome (GBS) known as acute inflammatory demyelinating polyneuropathy (AIDP), which appears to be an autoimmune disorder.
Guillain-Barré syndrome	Research suggests that there are four subtypes of GBS, and the causes can vary. Infection may be one notable culprit. For example, a recent infection with Campylobacter jejuni bacteria seems to cause GBS in about a quarter of people who are diagnosed.

Sometimes the symptoms will be similar to various conditions that cause damage to the myelin of your nerve cells. Here’s more detailed information about symptoms you might expect from these disorders.

Multiple sclerosis

MS causes a wide variety of symptoms that can range from mild to severe. Some people experience:

• severe fatigue
• numbness or tingling in the extremities
• difficulty walking and balancing
• vision problems
• speech difficulties known as dysarthria
• muscle spasticity
• tremors
• pain
• difficulty concentrating
• bowel and bladder dysfunction
• as many as 50 percent of people with MS also experience depression at some point in their lifetime

Optic neuritis

The most common symptoms include vision loss in one eye, pain around your eye that’s exacerbated by eye movement, and difficulty distinguishing between colors.

Transverse myelitis

Symptoms of transverse myelitis can include:

• weakness of the legs and arms
• pain in the lower back, arms, legs, or torso
• abnormal sensory feelings or even sensory loss
• bowel and bladder dysfunction

Acute disseminated encephalomyelitis

You may develop a number of symptoms, including:

• fever
• stiff neck
• fatigue
• balance issues
• weakness or tingling in your extremities
• blurred or double vision
• confusion

Neuromyelitis optica

Some people experience a single long-lasting attack, while others have a relapsing form of NMO.

Symptoms of NMO include:

• vision loss and eye pain in one or both eyes
• numbness, weakness, or even paralysis in arms or legs
• loss of bladder and bowel control

Adrenoleukodystrophy

Symptoms can vary, depending on what type of ALD you have.

Someone with childhood cerebral ALD may develop:

• muscle spasms
• seizures
• hearing problems
• vision deficits
• trouble with language comprehension

Someone with Addison’s disease may:

• lose their appetite
• experience weight loss
• develop weakness
• experience vomiting

Chronic inflammatory demyelinating polyneuropathy

With this condition, you may develop:

• progressive and symmetrical weakness, often around the muscles around your hips and shoulders, and also your hands and feet
• numbness, tingling, or prickling sensations
• fatigue
• double vision
• trouble swallowing

Guillain-Barré syndrome

GBS causes symptoms that can range from relatively mild weakness to paralysis. Some people might not even be able to breathe on their own without assistance. As many as 20 percent of people are left with significant disability.

Once a diagnosis is made, your doctor can begin discussing the most appropriate treatment for you.

Multiple sclerosis

There are a number of different FDA-approved preventive treatments for reducing the frequency and severity of MS symptoms, including:

• interferon beta-1a
• interferon beta-1b
• glatiramer acetate
• a monoclonal antibody known as natalizumab
• the chemotherapy agent mitoxantrone

Steroids are also prescribed for flare-ups or exacerbations. Recent research also suggests that it may be possible to repair the myelin if people have enough surviving oligodendrocyte cells, which wrap around the nerve cells, to begin making new myelin.

Optic neuritis

Sometimes optic neuritis symptoms will improve on their own, but your doctor may prescribe steroids to address the inflammation.

Transverse myelitis

Treatment may be given to address symptoms and reduce inflammation, and to address any infections that might be present. Possible treatments include:

• intravenous corticosteroid therapy
• plasma exchange therapy
• intravenous immunoglobin (IVIG)
• antivirals for any infections in the spinal cord
• pain medications to address both muscle and nerve pain

Neuromyelitis optica

Your doctor may prescribe corticosteroids or immunosuppressants to reduce symptoms. Another possible option is a process called plasmapheresis, which removes certain antibodies from your blood that may be contributing to the symptoms.

Acute disseminated encephalomyelitis

Intravenous steroids like methylprednisolone or oral steroids can help reduce the inflammation caused by ADEM. Plasmapheresis may also be an option with severe cases of this condition.

Adrenoleukodystrophy

One effective treatment for childhood ALD is hematopoietic stem cell transplant, which is a bone marrow transplant. People with Addison’s disease may experience some benefit from taking steroids. Some people may also take seizure medications or go to physical therapy to help with muscle spasms and weakness.

Chronic inflammatory demyelinating polyneuropathy

The most commonly used treatments include glucocorticoids, intravenous immunoglobulin (IVIg), and plasma exchange therapy to help modulate the immune system. Physiotherapy might help you build or maintain muscle strength and function, so you can be as mobile as possible.

Guillain-Barré syndrome

There’s no cure for GBS, but doctors may offer treatment such as high-dose immunoglobulin therapy (IVIg) or plasma exchange to ward off nerve damage. In the past, corticosteroid therapy was offered, but eventually research found it wasn’t effective.

10 tips for living well with a myelin sheath disorder

Living a normal life with a demyelinating disease can be challenging. You may encounter trouble seeing well and moving independently at times. These strategies for managing MS and other neurological diseases can help you live your life as fully as possible:

1. Use voice-to-text software. If you’re struggling with numbness, tingling, or muscle weakness in your hands and arms, don’t stress yourself even more by trying to write or type. This software can also be useful for anyone who’s having trouble seeing, due to inflammation of their optic nerves.
2. Use assistive devices or tools. There are devices that can make it easier to open jars or retrieve an item off a high shelf, or use a shower chair to sit upon if it’s too hard to stand.
3. Choose attire that’s easy to put on and take off. Velcro shoes aren’t just for little kids who can’t tie their shoes. They’re also useful for adults whose hands are weak or shaky. You might also appreciate elastic-waist pants or gadgets that help you pull up a zipper or fasten buttons. Stick with shoes with a sturdy tread so you’ll be less likely to slip.
4. See a little more clearly. You might try using a vision aid like a magnifying lens if your vision has been affected. Or if you’re experiencing double vision, or diplopia, talk to your doctor about prism glasses, which can help refract the light coming into your eyes to help you see better.
5. Use a cane. If you’re not as steady on your feet as you’d like to be, try using a cane to give you extra support. Supportive braces might also help. A motorized scooter or wheelchair might be another option to help you get around safely and confidently.
6. Rearrange your environment. Make your home work for you, rather than against you. Get rid of throw rugs that could trip you, and use non-skid bathmats in the bathroom. Store items that you use regularly within easy reach.
7. Practice good sleep hygiene. One of the best things you can do for yourself if you have a condition like MS is get a good night’s sleep. Simple strategies like going to bed each night at the same time, keeping your bedroom cool and dark, and taking time to wind down trying to sleep may help.
8. Eat a healthy diet. A 2016 randomized controlled trial found that people with MS who ate a low-fat, plant-based diet experienced lower levels of fatigue. Ask your doctor about making dietary changes to see if they improve your energy levels.
9. Seek out occupational therapy. If you’re experiencing muscle weakness, especially in your arms or hands, an occupational therapist may help with strategies.
10. Join a support group. You aren’t the only one with this disease. Finding a support group, either in person or online, can be a lifeline. You can talk about your challenges, listen to others, and learn strategies to make it easier to live with your disorder.

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Ongoing research, including research into stem cell therapies, may eventually bear fruit in the form of new effective treatments for a variety of disorders that affect the myelin covering of nerve cells.

In the meantime, communicating with your doctor about your symptoms, using strategies to help with your daily activities, and reaching out for support are good ways to manage your needs.

Myelin repair in multiple sclerosis methods

Many people ask the question: how to restore myelin and are there any drugs for this? In 2020, an article was published in the Lancet Neurology journal highlighting the latest scientific achievements in this direction:

https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30140-X/fulltext

Multiple sclerosis refers to demyelinating diseases, the prefix “de-” indicates destruction. At the same time, the physiological process of remyelination is going on in the brain, the prefix “re-” means restoration. Currently, we have almost two dozen drugs that belong to the group of drugs that change the course of multiple sclerosis (MRMS). DMT is aimed at slowing down and ideally at preventing the destruction of myelin, i. e. to slow down and stop the process of demyelination. At the same time, there are no registered drugs aimed at enhancing myelin recovery – remyelination. If you have a question: what is myelin for and what does it consist of? We refer you to our article on the website dedicated to the answer to this question: https://stopsclerosis.ru/rasseyannyj-skleroz/. In general, it can be said that myelin forms a sheath around the processes of neurons, provides nutrition for these processes and high-quality transmission of an electrical impulse through them.

So, in multiple sclerosis, the main target for immune cells is myelin and the cells that produce it – oligodendrocytes. At the same time, in areas with damaged myelin (indicated in red in the figure), the process of myelin restoration also occurs (indicated in blue in the figure):

We know that myelin is produced by oligodendrocytes. In the focus of demyelination, part of the oligodendrocytes die, but the part, mainly located on the border of the focus and intact tissue, remains intact. In these border zones, an active process of myelin restoration takes place. Secondly, new oligodendrocytes can also arise from their predecessors, which are located mainly in the subventricular zones near the ventricles of the brain. Such new oligodendrocytes can move to areas of damaged myelin and repair it, although this process is less intense than remyelination by preserved oligodendrocytes.

Thus, we can “feel” the points of application of the enhancement of the remyelination process: either by enhancing the activity of conditionally “old” oligodendrocytes preserved in the demyelination foci, or by enhancing the emergence of new, conditionally “young” oligodendrocytes from precursors. But there are two more ways to activate the recovery of myelin: an increase in the activity of neurons whose processes have lost myelin. Indeed, if the outgrowth of a neuron – the axon – loses myelin, then after a while it can collapse. If the axon continues to be active, then the remaining or new oligodendrocytes try to restore myelin for this particular axon in the first place. Finally, some immune cells, oddly enough, can enhance remyelination, such as regulatory T cells.

Indeed, a large number of scientific and clinical studies have been carried out and are currently being conducted on substances that can either stimulate existing oligodendrocytes to synthesize myelin, or enhance their formation of new oligodendrocytes:

But so far, none of the clinical studies have shown a really significant effect. For example, a study of bexarotene in patients with MS was recently completed. Unfortunately, this drug did not show any significant effect on the enhancement of remyelination:

https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(21)00179-4/

Therefore, we can unequivocally say that drug stimulation of myelin restoration processes is a matter of the future, but we think that it is very close.

At the same time, we should not forget about the third point of application of the enhancement of the myelin repair process: the activation of neurons whose axons have lost their processes. We can increase the activity of neurons by moving, involving various muscle groups, and performing complex motor acts. Here, neurorehabilitation comes to the fore: properly selected rehabilitation complexes can improve impaired functions, and the basis of such improvements is the activation of remyelination. Of course, neurorehabilitation does not replace, but only complements the use of DMTs, because it is precisely the right DMTs that allows you to slow down or stop the process of demyelination, and only after that you can try to enhance myelin recovery.

The fourth point of application of enhancing remyelination is the impact on certain subtypes of immune cells. With this approach, we can say that upon reaching a stable remission, the so-called NEDA state (no evidence of disease activity), remyelination processes are enhanced due to the more active work of regulatory immune cells. Therefore, the use of PMTRS allows not only to achieve suppression of the demyelination process, but also to enhance the processes of myelin restoration.

Chronic demyelinating polyneuropathies in clinical practice | Shirokov E.A.

Systemic symmetrical damage to peripheral nerves can be caused by metabolic disorders, ischemia, blood diseases, intoxication, alimentary factors, trauma, infections, allergic reactions, inflammatory and other pathological processes. The heterogeneity of the syndrome determines its wide prevalence – any doctor, specialist in therapeutic or surgical profile, inevitably faces this problem in his clinical practice. Accurate statistics reflecting the epidemiology of systemic damage to peripheral nerves do not exist. However, it can be safely assumed that the prevalence of polyneuropathies in the population is extremely high. Diabetes mellitus alone, which more often than other diseases leads to systemic damage to peripheral nerves, affects about 2 million people in the Russian Federation [1]. It is known that polyneuropathies associated with diabetes mellitus or alcohol intoxication account for more than two thirds of all cases of the disease [2].

Polyneuropathies are also characteristic of other pathological processes occurring with metabolic disorders. It would not be an exaggeration to assume that there are 4–5 million patients with clinical signs of polyneuropathy who require medical attention. Researchers increasingly include lesions of peripheral nerves in the structure of the metabolic syndrome. Surgical treatment of morbid obesity is becoming a common practice. Reconstruction of the gastrointestinal tract often saves patients from a number of fatal complications. However, subsequently, as a result of a violation of the process of assimilation of biologically important substances, these patients often suffer from disorders of the peripheral nervous system [1].
In textbooks, scientific articles and monographs, the authors use the terms “polyneuropathy” or “polyneuropathy” to characterize the systemic lesion of peripheral nerves. Probably, the term “polyneuropathy” (polyneuropathy) should be considered more correct – it is he who is mentioned in the Oxford Great Explanatory Medical Dictionary and the Encyclopedic Dictionary of Medical Terms. The concept of “polyneuropathy” seems to be broader, reflecting to a greater extent the fact of neuronal damage, including formations of the central nervous system.
There is no generally accepted classification of diseases and clinical syndromes based on dysfunction of peripheral nerves. According to the mechanism of development of the pathological process, inflammatory, toxic, allergic, traumatic and metabolic polyneuropathies are distinguished. There are acute and chronic forms of the disease [3].
Topical ideas about the nature of damage to the nervous system in polyneuropathy are fundamentally important – the pathological process is always limited to the formations of the peripheral nervous system. As a rule, signs of damage to the spinal cord or brain radically change the diagnostic concept and make one think of acute inflammatory diseases. Chronic metabolic polyneuropathies are usually limited to the involvement of peripheral nerves. If pathological changes affect the formation of the central nervous system, then the topological diagnosis expands and may include various forms of encephalo-, myelo-, radiculo-polyneuropathies [4]. Since such a refined topical diagnosis is the privilege of a neurologist, among endocrinologists and general practitioners, systemic lesions of the nervous system are often characterized as polyneuropathies.
The peripheral nervous system includes the posterior and anterior roots of the spinal cord, intervertebral spinal ganglia, spinal nerves, their plexuses, peripheral nerves, cranial nerves, as well as their roots and ganglia. Peripheral nerves are mostly mixed and consist of motor, sensory and vasomotor-secretory-trophic fibers. Although polyneuropathies may show predominantly motor and/or sensory disorders (sensory, motor), as a rule, upon careful examination, signs of damage to all nerve fibers that make up the peripheral nerve can be detected.
The nerve fiber, which is part of the peripheral nerve, consists of an axial cylinder located in the center, a myelin sheath that dresses the axial cylinder, and a Schwann sheath. Large nerve trunks consist of 800,000–1,000,000 nerve fibers, which provide a significant functional margin of safety for the peripheral nervous system. It is believed that the function of the nerve trunk is disturbed only in the case of the death of half of the nerve fibers.
The myelin sheath occupies a special place in the functioning of peripheral nerves. For many years it was believed that the myelin sheath plays the role of an electrical insulator in the process of conducting excitation along the nerve fiber. However, the role of the myelin sheath is probably more significant – it is directly involved in the formation of the electrical potential of the nerve fiber. The connective tissue in the peripheral nerves is represented by sheaths covering the nerve trunk (epineurium), its individual bundles (perineurium) and nerve fibers (endoneurium). Vessels supplying the nerve pass through the membranes. Thus, the peripheral nerve is a complex structure, the peculiarity of which lies in the unique spatial organization – the axon of one nerve cell, the body of which is located in the anterior horn of the spinal cord, reaches a meter in length!
The vulnerability of the formations of the peripheral nervous system is due precisely to these structural and functional features. Traumatic, infectious, vascular pathological factors easily manifest their effect on long nerve fibers, where damage in any area leads to dysfunction of the entire nerve. Myelin – a substance consisting of cholesterol, phospholipids and proteins – is the result of folate-dependent synthesis occurring with the direct participation of the enzyme methylenetetrahydrofolate reductase (MTHFR) and coenzymes (folic acid and B vitamins).
The myelin sheath is the most vulnerable part of the peripheral nerve. It suffers as a result of destruction (toxic, immune mechanisms) or insufficient synthesis of myelin components (metabolic disorders, lack of vitamins). In any case, the synthesis of myelin requires a significant tension of numerous enzyme systems, since the total mass of this substance in the body exceeds 200 g.
In the pathogenesis of metabolic polyneuropathy, disturbances in myelin synthesis play an important role. For example, in diabetes mellitus, high concentrations of glucose in the blood serum are accompanied by glycolysis of proteins, including enzymes involved in the synthesis of myelin. Alimentary deficiency of vitamins and folic acid in alcoholism disrupts the synthesis of myelin and, consequently, the function of nerve trunks. Myelin destruction (demyelination) often accompanies infectious and inflammatory processes. Demyelination (myelinopathy) means damage to the myelin sheaths while preserving the axons.
The most significant functional manifestation of demyelination is the blockade of conduction. Functional insufficiency in a blocked axon manifests itself in the same way as when crossing an axon. Despite the fact that the intersection of the nerve and the blockade of conduction during demyelination show similarities in the severity of the development of motor and sensory disorders, there are differences between them. So, with demyelinating neuropathies, the blockade of conduction is often transient and remyelination can proceed quickly over several days or weeks, often ending in recovery. The most important clinical sign of segmental demyelination is a dysfunction of the distal-peripheral type – the greater the length of the peripheral nerve, the more noticeable conduction disturbances become. First of all, this is manifested by disorders of sensitivity in the distal extremities.
So, dysfunction of long nerve trunks growing to the periphery determines the clinical manifestations of polyneuropathy. Sensitivity disorders in the form of hypoesthesia, hyperesthesia are the most common manifestations of polyneuropathy. With a more thorough examination, it is possible to detect disorders of deep types of sensitivity – joint-muscular, temperature. Neuropathic pain with elements of burning and irritation is the result of damage to nerve structures and can exist without an irritant [5]. Motor disturbances in polyneuropathy usually present with flaccid tetraparesis that initially involves the muscles of the feet and lower legs and then spreads proximally. In mild cases, paresis can be limited only to the legs, in which case it is important to differentiate it from damage to the roots of the cauda equina, in which the symptoms are usually asymmetric. In polyneuropathies, the extensor and abductor muscles are usually affected to a greater extent than the flexors and adductors. Paresis and paralysis in metabolic neuropathies are rare, but a decrease in periosteal-tendon reflexes can be found among the first symptoms. Vegetative-trophic disorders are manifested by dry skin, a decrease in muscle mass, the appearance of a “vascular network”.
The principles of treatment of chronic metabolic polyneuropathies are based on the correction of metabolic disorders. Stabilization of carbohydrate metabolism in diabetes mellitus brings the expected results, as well as the restoration of the function of the gastrointestinal tract in alcoholism.
Currently, complex treatment regimens for polyneuropathy use α-lipoic acid preparations, anticholinesterase drugs that improve nerve fiber conduction, vasoactive agents that improve microcirculation, and vitamins [6–8]. Vitamins play a special role, since folate-dependent myelin synthesis is impossible without B vitamins. Meanwhile, thiamine deficiency (vitamin B1) is considered one of the characteristic features of typical diseases of civilization [5]. A change in the nature of nutrition with an increase in the proportion of refined carbohydrates, a significant acidification of the internal environment due to a change in the structure of food – do not contribute to the absorption of thiamine, even if it is present in sufficient quantities in food. Meanwhile, B1 takes part in protein synthesis, regulation of fat and water-salt metabolism. Numerous studies have established that thiamine has antioxidant and immunomodulatory properties, is involved in the metabolism of the most important neurotransmitters – serotonin and γ-aminobutyric acid, acetylcholine. Being the main coenzyme of MTHFR, it is directly involved in the synthesis of myelin.
Vitamin B6 – pyridoxine, is a coenzyme of more than 100 enzymes, takes part in the synthesis of neurotransmitters (tryptophan, glycine, serotonin, dopamine, norepinephrine, adrenaline, histamine). It lowers the level of cholesterol, homocysteine ​​in the blood. Vitamin B6 controls erythropoiesis and is involved in the formation of the immune response. There is a convincing correlation between a decrease in the level of pyridoxine in the blood and the clinical manifestations of polyneuropathies.
Vitamin B12 (cyanocobalamin) is the main source of cobalt necessary for protein synthesis. B12 is directly involved in the synthesis of methionine and nucleic acids. It activates all types of metabolism: protein, fat and carbohydrate. It has been established that high concentrations of cyanocobalamin are necessary to prevent cognitive impairment (senile dementia), depression. The participation of B12 in the synthesis of myelin is its most important function.
Complex vitamin preparations are widely used in the treatment of patients with various diseases and pathological processes. But their most significant use is in diseases of the nervous system. Although the etiology of polyneuropathies is extremely diverse, the lack of B vitamins unites most of the clinical variants of this neurological syndrome. Recent studies demonstrate that thiamine deficiency develops in patients with diabetes mellitus due to its increased excretion by the kidneys. Replenishment of thiamine for diabetic patients is a task of daily practice. It has been established that the appointment of thiamine at a dose of about 300 mg per day in combination with vitamins B6 and B12 significantly reduces or eliminates the manifestations of polyneuropathy, primarily reducing neuropathic pain [2]. In addition to reducing the manifestations of sensitivity disorders, vitamins have a significant impact on the manifestations of vegetative-trophic disorders in the neuropathic form of diabetic foot syndrome.
Preparations containing vitamins in the required proportions are widely used in clinical practice. Trigamma (thiamine hydrochloride + pyridoxine hydrochloride + cyanocobalamin) is available in solution for intramuscular injection. Trigamma also contains lidocaine. The drug has a beneficial effect on inflammatory and degenerative diseases of the nerves and the motor apparatus. The use of the drug is indicated in the complex therapy of neuritis (including retrobulbar neuritis), neuralgia, myalgia, paresis of the facial nerve, radicular syndrome. With a pronounced pain syndrome, it is advisable to start treatment with an intramuscular injection (deep) of 2 ml of Trigamma daily for 5–10 days. with a transition in the future either to taking oral dosage forms, or to more rare injections (2-3 times a week for 2-3 weeks).
Many complex vitamin preparations can be used for long-term therapy in the recovery period. It must be remembered that folic acid should be used in the complex treatment of polyneuropathy along with B vitamins.
Thus, the treatment with vitamins in the complex therapy of diseases of the peripheral nervous system not only has not lost its significance, but has received a deeper justification. It should be considered as an unconditional indication the appointment of B vitamins in all cases of damage to the nervous system, which are based on the processes of demyelination or impaired remyelination. Modern correction of myelinopathies as systemic metabolic disorders is impossible without timely and adequate treatment with drugs containing thiamine, pyridoxine and cyanocobalamin. In diseases that occur with disorders of carbohydrate, fat and protein metabolism (diabetes mellitus), systematic treatment with vitamin preparations is necessary to activate metabolic processes, restore the processes of protein synthesis. Preparations containing vitamins are absolutely necessary for patients suffering from malabsorption of essential coenzymes (alcoholism, patients who have undergone complex reconstructive operations on the organs of the gastrointestinal tract). Correction of neurological manifestations can be successful with adequate treatment of the underlying disease, within which metabolic disorders develop.

Literature
1. Karpova E.V. Management of diabetes mellitus: new opportunities. – M.: Publishing house QUORUM, 2011. – 208 p.
2. Antsiferov M.B., Volkova A.K. Diagnosis and treatment of diabetic distal polyneuropathy in patients with diabetes mellitus in outpatient practice // RMJ. – 2008. – T. 16, No. 15. – S. 12–15.
3. Anisimova E.