Demyelination and Demyelinating Disease

Demyelinating diseases are those that lead to a loss of myelin, the sheaths of fatty tissue that surround and protect nerves so that they can send signals efficiently. A loss of myelin can cause neurological deficits, such as vision changes, weakness, altered sensation, and behavioral or cognitive (thinking) problems. 

Some demyelinating diseases affect the brain and/or spinal cord. Others affect the peripheral nerves that branch out from the brain and spinal cord. The most common demyelinating disease is multiple sclerosis (MS), an autoimmune disorder in which the immune system attacks myelin of the brain, spinal cord, and/or eyes. 

There are no cures for demyelinating diseases, but a variety of medical treatments can be used for successful management.

This article explains the symptoms and causes of demyelination and the tests that healthcare providers use to make a diagnosis. It also describes some common demyelinating disorders.

Symptoms of Demyelinating Disease

Myelin sheaths insulate peripheral nerves as well as nerves in the brain, spinal cord, and eyes. Each eye has an optic nerve that controls vision and carries signals to the brain. The myelin sheath function is to protect nerves and allow them to send signals efficiently.

When there is a deficiency or a sudden decrease in myelin, the nerves may become damaged and have difficulty sending signals, resulting in symptoms.

The symptoms of demyelination correspond to the affected area of the nervous system. For example, peripheral neuropathy affects the hands and feet in what is often described as a “stocking and glove” distribution.

Demyelination affecting the lower spine or the spinal nerves causes sensory changes or weakness of the legs. It may also diminish bowel and bladder control. Demyelination in the brain can cause a variety of problems, such as impaired memory or decreased vision.

Common symptoms of demyelinating diseases include:

• Bladder and/or bowel issues
• Chewing or swallowing difficulties
• Concentration lapses
• Coordination loss
• Fatigue
• Impaired memory
• Loss of or diminished vision
• Mood or behavioral changes
• Numbness or tingling in the hands, feet, arms, legs, or face 
• Slurred speech
• Walking difficulties
• Weakness in the arms or legs

Many types of MS are characterized by episodic symptoms and substantial improvement in between episodes. Peripheral neuropathy tends to gradually worsen. In some demyelinating conditions, such as cerebral adrenoleukodystrophy (CALD), the effects do not improve. In fact, they can be fatal.

Demyelinating Diseases and Their Causes

Demyelination is often caused by inflammation that attacks and destroys myelin. This can occur in response to an infection, or it can attack the body as part of an autoimmune process in which the immune system attacks healthy cells. Toxin exposure and some nutritional deficiencies can also cause or contribute to demyelination.

Sometimes demyelination occurs as a single episode, while other times it is ongoing.

Three categories of potential causes, detailed in the following sections, offer a sense of the wide array of possibilities. While the reasons some of these occur may be clear, other conditions can be idiopathic, meaning the reason behind them is unknown.

Demyelination can occur at any age, but each demyelinating condition tends to affect certain age groups. Genetics, health history, and exposures can also factor into one's risk.

Brain and Spinal Cord Diseases

Demyelination of the brain and spinal cord is often caused by inflammation due to autoimmune conditions or in response to viral infections. These diseases include:

• Multiple sclerosis: MS causes demyelination in the brain, spine, and/or optic nerve. There are several types of MS, and some are characterized by relapses and remissions while others are characterized by gradual decline. MS usually starts between the ages of 20 and 40. While it is manageable, it is a lifelong illness with no definitive cure.
• Transverse myelitis (TM): TM is an inflammation within the spinal cord that can cause demyelination and nerve damage. It generally leads to rapidly progressing muscle weakness or paralysis, beginning with the legs and sometimes moving to the arms. TM has many possible causes including viral infections, bacterial infections, and an abnormal immune response. It can also be a feature of MS.
• Neuromyelitis optica pectrum disorder (NOSD): Also called Devic's disease, NOSD is a severe inflammation of the optic nerve and spinal cord. It can sometimes affect the brain. NOSD is considered an autoimmune disease but its exact cause is unknown. NOSD leads to vision problems or blindness and muscle weakness or paralysis. It is usually a relapsing condition with inflammatory episodes that last weeks or month followed by periods of remission. Episodes often begin as eye pain followed by vision loss in one or both eyes or transverse myelitis.
• Acute disseminated encephalomyelitis (ADEM): ADEM is a rapidly progressive demyelinating episode. ADEM often affects young children. The symptoms are usually more intense than those of MS, and the condition typically resolves without lasting effects or a recurrence.
• Clinically isolated syndrome (CIS): CIS is a single episode that has all the characteristics of MS. Sometimes, CIS turns out to be the first episode of a relapsing form of MS, but then it often does not occur again. It is diagnosed in the same way as MS.
• Cerebral adrenoleukodystrophy (CALD): CALD is a severe genetic condition that mostly affects young boys. CALD causes vision loss and a profound loss of muscle control. The demyelination results from a defect in fatty acid metabolism that destroys myelin in early childhood. Treatments are limited, and CALD often results in early death. In September 2022, the Food and Drug Administration (FDA) approved Skysona (elivaldogene autotemcel), a one-time treatment to slow the progression of neurologic dysfunction in boys 4 to 17 years of age with early, active CALD. 
• Adrenomyeloneuropathy (AMN): AMN is a variant of CALD caused by the same gene. AMN predominantly affects young men, causing progressive weakness. There are two forms of AMN that vary in severity. One affects the spinal cord and may cause wheelchair dependence, but it is not fatal. The other type affects both the spinal cord and brain. In about 10% to 20% of those with brain involvement, AMN is severe and progressive and may lead to cognitive decline, behavioral changes, and death.
• Progressive multifocal leuokoencephalopathy (PML) : PML is a severe demyelinating disease and form of viral demyelination, meaning a virus causes the damage. PML occurs due to a reactivation of a virus (JC virus) that targets cells that make myelin. Most people have been exposed to JC virus, which can cause a mild cold. Reactivation tends to occur among people who have severe immune deficiency. It causes extensive brain involvement, often with permanent impairment.
• Balo’s disease: Also called concentric sclerosis, Balo's disease is considered a rare and progressive form of MS that usually develops in adulthood. Demyelination occurs throughout the brain and brain stem and can progress rapidly over weeks or more slowly over a few years. Symptoms vary based on areas of the brain affected but can include headaches, seizures, gradual paralysis, muscle spasms, or cognitive impairment.
  
• HTLV-1 associated myelopathy (HAM): Also called tropical spastic paraparesis (TSP), HAM is a disease of the spinal cord that occurs in some people infected with HTLV-1 virus. The virus, which is mostly found in tropical regions, is transmitted through blood or sexual contact. HAM affects less than 2% of those infected with HTLV-1. It can cause painful stiffness and weakness of the legs that progresses slowly over years. It may also lead to burning or prickling sensations or urinary incontinence, a loss of bladder control.

Peripheral Nerve Diseases

Like demyelination of the brain or spinal cord, demyelination of the peripheral nerves is often due to autoimmune disorders or viral infections. It can also be due to inherited conditions. Diseases in this category include:

• Optic neuritis: Optic neuritis is an inflammation of the optic nerve that often causes vision loss and eye pain, especially during eye movement. It has many causes, including viral infections such as measles or mumps. It can also be an early sign of MS.
• Hereditary demyelinating neuropathies: These are a group of inherited nerve conditions characterized by demyelination of the peripheral nerves. An example is Charcot-Marie polyneuropathy type 1. Patients usually present with slowly progressive weakness and numbness, initially affecting the lower legs and then the hands. Wasting (atrophy) of muscles is common.
• Guillain-Barré syndrome (GBS): GBS is an autoimmune disorder in which the body attacks the peripheral nerves. GBS causes weakness that begins in both feet, involving the legs and arms within a few days. GBS is a serious condition because it can cause weakness of the respiratory muscles that control breathing. Respiratory support with mechanical ventilation may be necessary. The condition typically affects adults over age 50. GBS is typically treated with intravenous immunoglobulin (IVIG), a therapy that suppresses the immune system, or with plasma exchange, a procedure that filters the blood. Either way, the prognosis is usually good.
• Chronic inflammatory demyelinating polyneuropathy (CIDP): CIDP is a recurrent form of GBS characterized by episodes of weakness. It is usually treated with IVIG or plasma exchange.

Deficiencies and Exposures

There are many other conditions that may cause or contribute to demyelination.

Vitamin deficiencies: Vitamins serve many functions in the body, including helping myelin production. Vitamin B12 deficiency can contribute to demyelinating disease of the spine as well as peripheral neuropathy.

Similar to B12 deficiency, copper deficiency can affect the spinal cord and peripheral nerves. Low copper can occur in those with a prior history of gastric surgery, excessive intake of zinc, or malabsorption.

Hypoxia, which is lack of oxygen in the body's tissues, can be caused by many medical conditions. Hypoxia due to cardiac arrest, heart attack, or depressed breathing from an overdose generally causes necrosis of the brain, or death of brain tissue. Recovery depends on the extent of the damage.

Medications and toxin exposures can temporarily damage myelin or may cause long-term damage. This can affect its function and production of new myelin. It can be very difficult to pinpoint the exact cause of toxin-induced demyelination. Once the offending agent is identified, reducing exposure is the key to recovery.

There are reports of demyelinating diseases, such as optic neuritis or ADEM, occurring in adults and children within a few days after they received a vaccine. The risk of inflammatory demyelination after vaccination is considered low and the number of documented cases, such as following flu vaccine or HPV vaccine, is small enough that it's often unclear if vaccines were the cause.

Diagnosing Demyelinating Disease and Demyelination

Demyelination is diagnosed using several different methods. A medical history and physical examination can often establish whether the brain, spine, optic nerves, or peripheral nerves are affected.

However, many possible diagnoses have similar signs and symptoms, so it may take some time to determine the exact type and cause of demyelination.

Clinical Examination

When you are being evaluated for a demyelinating illness, your healthcare provider may:

• Record your medical history and ask questions about how long you've had your symptoms, whether you've experienced them before, and whether you've been sick with an infection
• Ask you about other symptoms, such as pain, nausea, vomiting, or fevers: Your medical team will want to know about your history of other illnesses and your family medical history in general.
• Check your muscle strength, sensation, coordination, and ability to walk
• Check your vision and how your pupils react to light: You might have an ophthalmologic examination in which your healthcare provider looks at your eyes with an ophthalmoscope to see if you have optic neuritis (inflammation and demyelination of the optic nerve).

Imaging

Brain or spine imaging, such as demyelination magnetic resonance imaging (MRI) that uses a strong magnetic field and radio waves to produce two- or three-dimensional images, may be used to help identify areas of demyelination.

There are usually patterns of demyelination that correspond to different conditions.

Special Tests

Several non-invasive diagnostic tests can identify the effects of demyelination on the peripheral nerves or optic nerves:

• Electromyography (EMG): Thin needle electrodes are inserted through the skin into muscles to measure muscle activity during rest and movements. This test is slightly uncomfortable, but it is safe, and any discomfort resolves once the test is completed.
• Nerve conduction studies (NCV): This test measures how fast the nerves conduct electrical signals. It involves direct stimulation of the nerve by shock-emitting electrodes that are placed on the skin directly over the nerve. An NCV examination can be slightly uncomfortable, but it is safe, and the discomfort stops after the examination is over. EMG and NCV are often used together for a diagnosis. If you are having both tests, the NCV is typically done first.
• Evoked potentials: These tests measure the response of the brain to certain stimuli. Visual evoked potentials, for example, measure the brain’s response to lights and other visual stimuli.
• Lumbar puncture (LP): Also often referred to as a spinal tap, a lumbar puncture involves inserting a needle into the lower back to collect a sample of cerebrospinal fluid (CSF) that cushions your spinal cord and brain. The fluid often shows signs of infection or inflammatory disease, and the results can be used to assist in the diagnosis of demyelinating conditions. The test takes about 10 to 20 minutes and may be slightly uncomfortable.
  

Treatment of Demyelinating Diseases

The treatment of demyelination depends on the condition. Given the possible diagnoses, it's easy to see how widely treatments can differ.

Regardless, though, treatment is focused on management of symptoms and preventing further demyelination.

Typically, myelin regenerates on its own. If there is little or no nerve damage, symptoms can resolve and neurological recovery is possible. At present, there is no treatment that can restore or rebuild myelin.

Some of the tactics that may help prevent demyelination include immunosuppression, use of supplements for nutritional deficiencies, treatment of symptoms, and rehabilitation therapies.

Immunosuppression

Treatments may be aimed at blocking or suppressing the pathways which can lead to inflammation. For example, since multiple sclerosis is chronic, it is managed with MS disease-modifying therapy (DMT). Steroids and DMTs work by suppressing the immune system to prevent an inflammatory attack on the myelin.

Avoiding Toxins

If a medication or toxin exposure is identified as a cause of demyelination, it should be avoided if possible. This probably won't reverse symptoms but can prevent further neurological damage.

Supplements

The use of supplements can be helpful to restore nutritional deficiencies. For example, a lack of vitamin B12 and copper have been linked to demyelination, so they can play an important role in treatment.

Symptomatic Treatment

Treatment can be tailored to a specific symptoms. For example, some people need medication to ease pain or discomfort. Medication can also help control symptoms such as anxiety or depression. For other people, bladder dysfunction can improve with medication.

Rehabilitation

Physical therapy, speech or swallow therapy, and balance therapy are examples of the types of rehabilitation that can help someone recover from or cope with a demyelinating illness.

Statins and Demyelinating Disease

Statins, which are cholesterol-lowering medications, are sometimes considered as an add-on treatment for demyelinating diseases, such as MS, to try to slow disease progression. However, research is lacking or shows no benefit.

For example, a 2022 systematic review and meta-analysis on statin use in MS found no benefit in those using statins as an add-on treatment for relapsing-remitting MS, a common type of MS that involves flare-ups followed by periods of remission. The researchers concluded that more studies are needed on statin use in those with other forms of MS.

Summary

Demyelinating diseases are often caused by inflammation that attacks and destroys nerves' protective myelin sheaths. Inflammation can occur in response to an infection, or it can attack the body as part of an autoimmune process.

Toxins or infections can also harm myelin or may interfere with its production. A lack of myelin formation can also be caused by certain nutritional deficiencies.

The symptoms of demyelination correspond to the affected area of the nervous system. Treatment depends on the condition behind the demyelination.