Demyelination

  105        

Demyelination is a term that refers to the disorder of the structure of the myelin sheath that covers the axons of neurons in the brain and spinal cord. Diseases that occur as a result of demyelination are called demyelinating diseases.

Key points:

  • Myelin serves as an insulator for axons, the axons being the fibers from which nerves are formed.
  • Axons that are affected by demyelination drive nerve impulses much more slowly than normal axons.
  • Demyelination most commonly affects neurons in the spinal cord, optic nerves, and white matter in the brain.
  • Demyelination is the cause of such a serious disease as multiple sclerosis.

In this article you will find out what are the causes of demyelination, what symptoms cause demyelination, in what diseases demyelination can be encountered and how it can be diagnosed and treated.

Demielinizare

What is demyelination?

Demyelination is the destruction of the myelin sheath.

For a deeper understanding of demyelination, it is necessary to know what the structure of neurons (nerve cells) is and how the nerve impulse is transmitted.

Neurons are made up of three main parts:

  • body of the neuron (soma): is the central part of the neuron where the nucleus and all other important structures are needed to provide nutrients and energy to the cell.
  • dendrites: are branches of the neuron's body. Dendrites have the function of transmitting impulses received from other neurons to the body of the neuron.
  • axon: is the longest branch of the neuron (some axons can be longer than 1 m). The main function of the axon is to transmit the nerve impulse from the body of the neuron to other neurons.

Most neurons are covered by a layer of fat (phospholipids) called the myelin sheath. The myelin sheath covers the axon in a segmented manner. Between the myelin segments are bare portions of the axon, called Ranvier nodules.

This specific structure of the axon plays a very important role in how the nerve impulse is transmitted from one neuron to another.

Understanding the connection between the way the myelin sheath is organized and the speed with which the nerve impulse is conducted is essential to understand why demyelination (disorganization of this structure) can cause the symptoms we will talk about below.

Normally, the electrical impulse moves across the cell membrane through continuity. For visualization, we can use the analogy with moving a train on a railway line. The train stops at each station on the way, and cannot reach the next station without going through all the stations that precede it.

On the membrane of a normal cell these stations, which represent channels in the cell membrane, are located very close to each other. The passage of a membrane segment by an electrical impulse will require a very large number of "stops".

The myelin sheath covers (“closes”) all the “stations” in the myelinated portions of the axon and leaves open only the “stations” in the uncovered portions. Now, the same nerve impulse can reach its destination by stopping at far fewer stations, spending less time stationary and therefore at a higher speed.

This mode of propagation of the electrical impulse is called saltatory, when the impulse "jumps" from one Ranvier node to another, without passing through the segments located between these nodes.

This is the most important mission of the myelin sheath, reducing the number of stations along the entire pulse path.

Following demyelination, the myelin sheath disappears on certain parts of the axon, discovering a very large number of "stations". Once in these demyelinated portions, the nerve impulse will slow down, trying to get through each of them. Below is illustrated this process of slowing down the nerve impulse in the demyelinated portions of the axon.

demielinizare

Another no less important function of the myelin sheath is the isolation of the axon. Imagine that the axon is nothing more than an electric cable, whose function, of course, is to conduct electricity. Each cable has an insulating sheath. The insulation of the cable is done not only for safety reasons, but also for energy conservation. Without it, much of the electricity will be lost on contact with other objects.

Demyelination of the axons, similarly, will cause much of the nerve impulses to be lost in the surrounding tissues. Thus the nerve impulse may decrease or even be completely lost, if the demyelinating portions will be particularly large.

Adding all this, we understand that demyelination is the loss of the myelin sheath on certain segments of the axon, which leads to slowing and decreasing in intensity of the nerve impulse.

What are the causes of demyelination?

Demyelination can have several causes. Like any body structure, it can be influenced by certain external as well as internal factors.

If demyelination is a result of a disorder of the myelin formation process, this type of demyelination is called leukodystrophic. In this case, the myelin is destroyed due to its defective structure, which makes it less durable and fragile.

If demyelination is the result of the destruction of normal myelin sheaths, then this type of demyelination is called myelinoclastic.

Some types of demyelination have a well-established cause (viral infection, intoxication, inflammation), while for other types of diseases accompanied by demyelination a well-established cause is not known (eg multiple sclerosis).

There are a number of diseases, in which demyelination has a hereditary character.

Viruses

Certain viruses are known to attack the myelin sheath and cause demyelination. The best known of these are:

  •      HTLV-1 virus
  •      John Cunningham virus (JC virus)
  •      Measles virus

When one of the viruses capable of inducing demyelination enters the body, a number of demyelinating diseases can occur. Below are some of the best known of these.

Progressive multifocal leukoencephalopathy

This demyelinating disease is fatal. Demyelination in this case is caused by infection with the JC virus. More frequently, progressive multifocal leukoencephalopathy occurs in patients whose immune system is weakened (administration of immunosuppressive drugs or suppression of the immune system against other diseases, such as leukemias and lymphomas).

The JC virus is widespread and most people are carriers of this virus (similar to the herpes virus). As with herpes viruses, the immune system inhibits this virus and does not allow it to affect us in one way or another.

This is why progressive multifocal leukoencephalopathy can only occur if the immune system is very weakened, and is no longer able to control the activity of the virus.

Subacute sclerosing panencephalitis

Another demyelinated disease that is caused by viral infection is subacute sclerosing panencephalitis. This disease usually appears a few years after a measles infection.

Children are more commonly affected. It has been shown that with the decrease of the age at which the child was infected with measles, the risk of demyelination also increases.

Tropical spastic paraparesis and myelopathy associated with HTLV-1

In these two diseases, demyelination occurs in the spinal cord. The cause of these diseases, as the name suggests, is HTLV-1 virus infection. More frequently this type of demyelination was found in Japan, in the Caribbean basin, South America, Africa.

Intoxication

Certain substances can affect the myelin sheath and cause demyelination.

Organophosphorus substances, which are contained in commercial insecticides, can damage the myelin sheath.

Carbon monoxide poisoning has also been associated with demyelination. In this case, the role of hypoxia (lack of oxygen in the tissues) is also mentioned as a factor that can degrade the myelin sheath.

Some neuroleptics, drugs used to treat psychiatric conditions, have the potential to cause demyelination.

Inflammatory demyelination

Inflammation of the nervous system can be a cause of demyelination. Several diseases are known to be accompanied by inflammatory demyelination:

  •      Multiple sclerosis,
  •      Acute disseminated encephalomyelitis, and
  •      Acute hemorrhagic leukoencephalopathy.
  •      Transverse myelitis
  •      Optic neuromyelitis (Devic's disease)
  •      Schilder's disease

Demyelination in these diseases is the result of a disorder of the immune system. Immune cells (T lymphocytes) begin to attack the myelin sheath, considering it foreign to the body. This occurs as a result of a mistake by the immune system recognizing one's own tissues. For example, infection with a myelin-like structural virus can cause the immune system to identify myelin as a virus and destroy it, leading to demyelination.

Ischemic demyelination

Ischemia is a term that means a decrease in the blood supply to certain tissues. Sometimes disorders of the blood supply to the brain tissue can cause demyelination. Myelin that does not receive enough nutrients and oxygen is subject to destruction. Thus ischemic demyelination occurs.

One of the characteristic diseases for this group is autosomal dominant cerebral arteriopathy with subcortical infarctions and leukoencephalopathy, or, more simply, CADASIL.

Demyelination due to the formation of abnormal myelin

There are some very rare diseases in which myelin is destroyed due to its abnormal structure. These diseases appear in early childhood. In the body of these children some enzymes involved in the formation of myelin are defective or missing.

Metachromatic leukodystrophy - occurs from a defect in the enzyme called aryl sulfatase.

Adrenoleukodystrophy - is the result of a defect in the formation of fats (very long chain fatty acids) that are a component part of myelin.

Krabbe leukodystrophy - in this disease the defect occurs in the enzyme called galactosylceramidase.

Nutritional deficiencies

A series of deficiencies of certain elements or nutrients, as an important rule for the synthesis and functioning of the myelin sheath, can make the synthesized myelin structurally abnormal, fragile and, as a result, destroyed.

One of the best known deficiencies associated with demyelination is vitamin B12 deficiency. Vitamin B12 plays an important role in the formation of the myelin sheath.

Demyelination caused by vitamin B12 deficiency typically affects the spinal cord.

In recent years, copper deficiency has been proposed as a possible cause of demyelination of the central nervous system.

Copper deficiency can lead to demyelination in the spinal cord, demyelination of peripheral nerves and optic nerve.

What are the symptoms of demyelination?

Given that demyelinating lesions can theoretically occur in any region of the central and peripheral nervous system where myelin nerve fibers are contained, the symptoms of demyelination can also be extremely varied.

However, due to mechanisms that are not yet fully known, demyelination occurs predominantly in well-defined regions of the nervous system. Thus, a picture more or less common to most diseases characterized by demyelination was made.

First, if we remember the connection between demyelination and neuronal axon function, it is easy to understand why most of the symptoms of demyelination are deficient.

Poor neurological symptoms are those symptoms that occur as a result of decreased neuronal function or as a result of decreased number of neurons responsible for a particular function.

The reduction in driving speed results in a reduced intake of nerve impulses in a certain unit of time, as well as a delayed reaction speed to a certain stimulus.

How this translates into clinical signs and symptoms we will see below.

Vision disorders

  • if demyelination has reached the optic nerve (the nerve that connects the retina and the region of the brain responsible for image analysis) it is possible to blur vision, loss of parts of the visual field.
  • if the nerve that controls the functioning of the eyeball muscles (which correctly positions the eyeballs) is affected, diplopia is possible - doubling the image.

Coordination disorders

Demyelination very often affects the structures of the nervous system involved in coordinating movements. These structures begin with the cerebellum (a region of the brain responsible for the spatial positioning of the body) and the frontal lobe (a region of the brain that is responsible for initiating and performing movements), pass through the spinal cord, and end in the motor nerves.

In case of demyelination in the cerebellum the following symptoms are possible:

  • Astasia - the inability to stay upright
  • Abasia - the difficulty of correctly assessing the center of gravity. The patient is forced to increase the support surface (legs wide apart) or to lean on the supports.
  • Ataxia - a severe gait disorder, in which the patient's gait resembles that of a drunk man. This gait is called cerebellar gait. Patients in this case seem to run after the center of gravity, the movements are jerky, there is a lack of coordination between the movements of the upper and lower limbs.

Muscle symptoms

Demyelinating lesions in the frontal lobe may cause the following symptoms:

  • Changes in muscle tone - the most common is an increase in muscle tone, taking the form of spasticity. The muscles appear to be made of wood and are difficult to undergo passive movements.

Sphincter symptoms

Demyelination of the spinal cord can be manifested by:

  • Sphincter disorders - most common in the case of demyelinating lesions are disorders of emptying the bladder. The patient has difficulty removing urine due to increased bladder sphincter tone. The bladder sphincter is the muscle responsible for retaining urine in the bladder until urination, when it relaxes.

Demyelination of peripheral nerves

In the case of demyelination of the peripheral nerves, symptoms may vary depending on the type and location of the damaged nerves, ranging from total loss of muscle strength in Guillain-Barre syndrome, to sensitivity disorders and disorders of the vegetative system in chronic demyelinating neuropathies (CIDP).

How can demyelination be diagnosed?

Demyelination occurs when the normal structure of neurons in particular, and of nervous system tissues in general, is altered. At the same time, these changes in structure lead to some changes in the functions of the nervous system. Finally, the cause that led to all these changes also leaves traces in our body.

To establish a diagnosis of demyelinating disease, doctors may indicate examinations and tests that will identify changes in the structure of the nervous system, deviations from its normal functioning, and will also indicate certain investigations that will be directed to identify the cause that will be guilty of the changes mentioned above.

To see if the structure of the tissues has undergone any specific changes for demyelination, Magnetic Resonance Imaging (MRI) is frequently used. MRI is a method of non-invasive visualization of body structures. This investigation allows the identification of regions of the nervous system in which signs of demyelination have appeared.

The specific signs of demyelination that can be seen on an MRI examination vary depending on the exact type of MRI examination, but in most cases they show regions of relatively small size (from a few millimeters to 1 cm) where tissue density is increased. These changes are called hyperintensities, since on an MRI image they appear brighter than normal tissue.

With the destruction of myelin, the body tries to repair the defects caused by demyelination. Destroyed myelin is replaced by newly formed myelin. This process is called remyelination. The problem is that the newly formed myelin, in turn, is defective, and differs structurally (it is denser) and functionally from normal myelin.

When in a region affected by demyelination remyelination leads to the formation of a large volume of abnormal myelin, it occurs on MRI as a thickening of normal nerve tissue. These specific changes for demyelination, seen on MRI, are called plaques.

A diagnostic method called recording evoked potentials is used to detect deviations from the normal functioning of the nervous system.

Evoked potentials are responses of the nervous system that normally occur (are evoked) after a certain stimulus. If the time after which a (potential) response to a stimulation is measured, in patients with demyelination this time will be longer (remember the effects of demyelination on the speed at which the nerve impulse is transmitted?).

The evoked potentials as a rule are recorded by such methods as electroencephalography (recording of the response in the cerebral cortex) or electromyography (recording of the response in peripheral muscles and nerves).

Cerebrospinal fluid analysis is often used to identify a cause of demyelination (if an infectious cause is suspected). Sometimes this analysis allows the identification of certain changes in the cerebrospinal fluid that can talk about the changes that take place in the nervous tissue and can help establish a diagnosis of demyelinating disease.

The cerebrospinal fluid is the aqueous medium that covers the brain and spinal cord. Therefore many changes that occur in the nervous tissue frequently lead to characteristic changes in the cerebrospinal fluid. This allows us to analyze these changes and judge indirectly about the processes that take place in the nervous tissue.

How can demyelination be treated?

The treatment of demyelination remains a difficult problem that a very large number of researchers are working on today.

While some types of demyelination, such as those with a well-established cause (intoxication, nutritional deficiencies) can be eliminated by compensating for deficiencies or eliminating the toxin, other types of demyelination still have no cure.

In the vast majority of cases the treatment is symptomatic.

Treatment aimed at modulating the function of the immune system is used to control the evolution of inflammatory and autoimmune diseases accompanied by demyelination.

Share