Multiple sclerosis (MS) is the most common disabling neurological disease of young adults with symptom onset generally occurring between the ages of 20 to 40 years.
In MS, the immune system cells that normally protect us from viruses, bacteria, and unhealthy cells mistakenly attack myelin in the central nervous system (brain, optic nerves, and spinal cord). Myelin is a substance that makes up the protective sheath (myelin sheath) that coats nerve fibers (axons).
MS is a chronic disease that affects people differently. A small number of people with MS will have a mild course with little to no disability, whereas others will have a steadily worsening disease that leads to increased disability over time. Most people with MS, however, will have short periods of symptoms followed by long stretches of relative quiescence (inactivity or dormancy), with partial or full recovery. The disease is rarely fatal and most people with MS have a normal life expectancy.
Myelin and the immune system
MS attacks axons in the central nervous system protected by myelin, which are commonly called white matter. MS also damages the nerve cell bodies, which are found in the brain's gray matter, as well as the axons themselves in the brain, spinal cord, and optic nerves that transmit visual information from the eye to the brain. As the disease progresses, the outermost layer of the brain, called the cerebral cortex, shrinks in a process known as cortical atrophy.
The term multiple sclerosis refers to the distinctive areas of scar tissue (sclerosis—also called plaques or lesions) that result from the attack on myelin by the immune system. These plaques are visible using magnetic resonance imaging (MRI). Plaques can be as small as a pinhead or as large as a golf ball.
The symptoms of MS depend on the severity of the inflammatory reaction as well as the location and extent of the plaques, which primarily appear in the brain stem, cerebellum (involved with balance and coordination of movement, among other functions), spinal cord, optic nerves, and the white matter around the brain ventricles (fluid-filled cavaties).
Signs and symptoms of MS
The natural course of MS is different for each person, which makes it difficult to predict. The onset and duration of MS symptoms usually depend on the specific type but may begin over a few days and go away quickly or develop more slowly and gradually over many years.
There are four main types of MS, named according to the progression of symptoms over time:
Relapsing-remitting MS—Symptoms in this type come in the form of attacks. In between attacks, people recover or return to their usual level of disability. When symptoms occur in this form of MS, it is called an attack, a relapse, or exacerbation. The periods of disease inactivity between MS attacks are referred to as remission. Weeks, months, or even years may pass before another attack occurs, followed again by a period of inactivity. Most people with MS are initially diagnosed with this form of the disease.
Secondary-progressive MS—People with this form of MS usually have had a previous history of MS attacks but then start to develop gradual and steady symptoms and deterioration in their function over time. Most individuals with severe relapsing-remitting MS may go on to develop secondary progressive MS if they are untreated.
Primary-progressive MS—This type of MS is less common and is characterized by progressively worsening symptoms from the beginning with no noticeable relapses or exacerbations of the disease, although there may be temporary or minor relief from symptoms.
Progressive-relapsing MS—The rarest form of MS is characterized by a steady worsening of symptoms from the beginning with acute relapses that can occur over time during the disease course.
There are some rare and unusual variants of MS, such as:
Marburg variant MS (also known as malignant MS) causes swift and relentless symptoms and decline in function, and may result in significant disability or even death shortly after disease onset.
Balo's concentric sclerosis causes concentric rings of myelin destruction that can be seen on an MRI and is another variant type of MS that can progress rapidly.
Early MS symptoms often include:
Vision problems such as blurred or double vision, or optic neuritis, which causes pain with eye movement and rapid vision loss
Muscle weakness, often in the hands and legs, and muscle stiffness accompanied by painful muscle spasms
Tingling, numbness, or pain in the arms, legs, trunk, or face
Clumsiness, especially difficulty staying balanced when walking
Bladder control problems
Intermittent or constant dizziness
MS may also cause later symptoms, such as:
Mental or physical fatigue which accompanies the early symptoms during an attack
Mood changes such as depression or difficulty with emotional expression or control
Cognitive dysfunction—problems concentrating, multitasking, thinking, learning, or difficulties with memory or judgment
Muscle weakness, stiffness, and spasms may be severe enough to affect walking or standing. In some cases, MS leads to partial or complete paralysis and the use of a wheelchair is not uncommon, particularly in individuals who are untreated or have advanced disease. Many people with MS find that weakness and fatigue are worse when they have a fever or when they are exposed to heat. MS exacerbations may occur following common infections.
Pain is rarely the first sign of MS but pain often occurs with optic neuritis and trigeminal neuralgia, a disorder that affects one of the nerves that provides sensation to different parts of the face. Painful limb spasms and sharp pain shooting down the legs or around the abdomen can also be symptoms of MS.
Conditions associated with MS
Transverse myelitis (an inflammation of the spinal cord) may develop in those with MS. Transverse myelitis can affect spinal cord function over several hours to several weeks before partial or complete recovery. It usually begins as a sudden onset of lower back pain, muscle weakness, abnormal sensations in the toes and feet, or difficulties with bladder control or bowel movements. This can rapidly progress to more severe symptoms, including arm and/or leg paralysis. In most cases, people recover at least some function within the first 12 weeks after an attack begins.
Neuromyelitis optica is a disorder associated with transverse myelitis as well as optic nerve inflammation (also known as optic neuritis). People with this disorder usually have abnormal antibodies (proteins that normally target viruses and bacteria) against a specific channel in optic nerves, the brain stem or spinal cord, called the aquaporin-4 channel. These individuals respond to certain treatments, which are different than those commonly used to treat MS.
Trigeminal neuralgia is a chronic pain condition that causes sporadic, sudden burning or shock-like facial pain. The condition is more common in young adults with MS and is caused by lesions in the brain stem, the part of the brain that controls facial sensation.
Who is more likely to get multiple sclerosis?
Females are more frequently affected than males. Researchers are looking at several possible explanations for why the immune system attacks central nervous system myelin, including:
Fighting an infectious agent (e.g., a virus) that has components that mimic components of the brain (molecular mimicry)
Destroying brain cells because they are unhealthy
Mistakenly identifying normal brain cells as foreign
There is also something known as the blood-brain barrier, which separates the brain and spinal cord from the immune system. If there is a break in this barrier, it exposes the brain to the immune system. When this happens, the immune system may misinterpret structures in the brain, such as myelin, as “foreign.”
Research shows that genetic vulnerabilities combined with environmental factors may cause MS.
At What Age Does MS Usually Start?
The first symptoms often start between ages 20 and 40. Most people with MS have attacks, also called relapses, when the condition gets noticeably worse. They’re usually followed by times of recovery when symptoms improve. For other people, the disease continues to get worse over time.
In recent years, scientists have found many new treatments that can often help prevent relapses and slow the disease’s effects.
Types of MS
There are three main types of MS:
Relapsing-Remitting MS (RRMS)
It’s the most common type of MS. About 85% of people with MS get this diagnosis. With RRMS, you tend to get temporary flare-ups. These are called relapses. If you have RRMS, you’re very likely to get worsening symptoms during an attack.
After the flare-up, you go through a phase of remission – it’s a period of time when you don’t have symptoms. However, your condition doesn’t get worse during remission.
Primary-Progressive MS (PPMS)
If you have PPMS, your MS symptoms tend to slowly worsen from the time you’re diagnosed. But you don’t get specific periods of relapses or remission. About 10% of people with MS get diagnosed with PPMS.
Secondary-Progressive MS (SPMS)
With SPMS, your symptoms steadily get worse over time. You might develop this type after you develop early RRMS symptoms.
Genetic susceptibility
MS itself is not inherited, but susceptibility to MS may be inherited. Studies show that some individuals with MS have one or more family member or relative who also have MS.
Current research suggests that dozens of genes and possibly hundreds of variations in the genetic code (gene variants) combine to create vulnerability to MS. Some of these genes have been identified, and most are associated with functions of the immune system. Many of the known genes are similar to those that have been identified in people with other autoimmune diseases as type 1 diabetes, rheumatoid arthritis, or lupus.
Infectious factors and viruses
Several viruses have been found in people with MS, but the virus most consistently linked to the development of MS is the Epstein-Barr virus (EBV) which causes infectious mononucleosis.
Only about five percent of the population has not been infected by EBV. These individuals are at a lower risk for developing MS than those who have been infected. People who were infected with EBV in adolescence or adulthood, and who therefore develop an exaggerated immune response to EBV, are at a significantly higher risk for developing MS than those who were infected in early childhood. This suggests that it may be the type of immune response to EBV that may lead to MS, rather than EBV infection itself. However, there is still no proof that EBV causes MS and the mechanisms that underlie this process are poorly understood.
Environmental factors
Several studies indicate that people who spend more time in the sun and those with relatively higher levels of vitamin D are less likely to develop MS or have a less severe course of disease and fewer relapses. Bright sunlight helps human skin produce vitamin D. Researchers believe that vitamin D may help regulate the immune system in ways that reduce the risk of MS or autoimmunity in general. People from regions near the equator, where there is a great deal of bright sunlight, generally have a much lower risk of MS than people from temperate areas such as the U.S. and Canada.
Studies have found that people who smoke are more likely to develop MS and have a more aggressive disease course. Indeed, people who smoke tend to have more brain lesions and brain shrinkage than non-smokers.
Sources:
https://lonestarneurology.net/neurological-disorders/multiple-sclerosis/
https://www.ninds.nih.gov/health-information/disorders/multiple-sclerosis
Prepared by Viktorija Stučytė based on online sources
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